Imidazoles are tunable nucleofuges for developing tyrosine-reactive electrophiles

Abstract

Sulfonyl-azole compounds (e.g., sulfonyl-imidazole compounds) and their use as covalent ligands for reactive nucleophilic amino acid residues in proteins, such as reactive tyrosines, e.g., to selectively form modified proteins and / or to alter the biological activity of the proteins are described. Sulfonyl-imidazole compounds for inhibiting particular proteins, such as prostaglandin reductase 2 (PTGR2) and glutathione S-transferase (GST) enzymes, are also described.

Description

[0001]Attorney Docket No.: 3062 / 203 PCT DESCRIPTION IMIDAZOLES ARE TUNABLE NUCLEOFUGES FOR DEVELOPING TYROSINE- REACTIVE ELECTROPHILES CROSS REFERENCE TO RELATED APPLICATION This application claims benefit of U.S. Provisional Application Serial No.63 / 653,616 filed May 30, 2024, the disclosure of which is incorporated herein by reference in its entirety. GRANT STATEMENT This invention was made with government support under Grant Nos. GM144472 and AI169412 awarded by National Institutes of Health. The government has certain rights in the invention. TECHNICAL FIELD The presently disclosed subject matter relates to sulfonyl-heterocycle compounds, e.g., sulfonyl-imidazole compounds, and their use as electrophiles for covalently reacting with nucleophiles, such as nucleophilic side groups of amino acids. In some embodiments, the presently disclosed subject matter relates to sulfonyl-imidazole compounds their ability to act as selective inhibitors of prostaglandin reductase 2 (PTGR2) and glutathione-S-transferase (GST) enzymes. BACKGROUND Small molecules can serve as versatile tools for perturbing the functions of proteins in biological systems. Many human proteins currently lack selective chemical ligands; and there are several classes of proteins that are currently considered as undruggable. Covalent ligands offer a strategy to expand the landscape of proteins amenable to targeting by small molecules. In some instances, covalent ligands combine features of recognition and reactivity, thereby providing for the targeting of sites on proteins that are difficult to address by reversible binding interactions alone. For example, sulfonyl-triazoles have emerged as a reactive group for covalent modification of tyrosine sites on proteins through sulfur-triazole exchange (SuTEx) chemistry. See PCT International Publication No. 2020 / 214336, the disclosure of which is incorporated by reference in its entirety. However, there remains an ongoing need for additional covalent probes and ligands for use in the investigation of the function of enzymes and other proteins, and in the development of therapeutic compounds that can modulate protein activity. In particular, there is an ongoing Attorney Docket No.: 3062 / 203 PCT need for additional small molecule covalent protein inhibitors with enhanced selectivity for the development of therapeutics with decreased off-target effects. SUMMARY This Summary lists several embodiments of the presently disclosed subject matter, and in many cases lists variations and permutations of these embodiments. This Summary is merely exemplary of the numerous and varied embodiments. Mention of one or more representative features of a given embodiment is likewise exemplary. Such an embodiment can typically exist with or without the feature(s) mentioned; likewise, those features can be applied to other embodiments of the presently disclosed subject matter, whether listed in this Summary or not. To avoid excessive repetition, this Summary does not list or suggest all possible combinations of such features. In some embodiments, the presently disclosed subject matter provides a compound having a structure of Formula (I) or Formula (I’): wherein: G2 is selected from the group comprising H, halo, alkyl, substituted alkyl, perhaloalkyl, aralkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; G3 is Oˉ or alkyl, optionally methyl; G4is selected from the group comprising alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocycyl, aralkyl, substituted aralkyl, substituted aryloxy, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; and Aˉ is present or absent, wherein when G3 is alkyl, Aˉ is present and is an anionic group, optionally trifluoromethanesulfonate anion (OTf), and where G3is Oˉ, Aˉ is absent. In some embodiments, G4is substituted phenyl, optionally wherein G4is phenyl substituted with alkoxy or a group having the structure -C(=O)-R, optionally wherein R is amino, alkylamino, dialkylamino, or an optionally substituted nitrogen-containing heterocycle. Attorney Docket No.: 3062 / 203 PCT In some embodiments, G2 is selected from halo, trifluoromethyl, aryl, and heteroaryl, optionally pyridyl. In some embodiments, G2 is selected from 2-pyridyl and 3-pyridyl. In some embodiments, the compound of Formula (I) has a structure of Formula (IIa) or (IIb): wherein: G2 is as defined for Formula (I); and R1 is selected from aryl, heteroaryl, substituted aryl, or substituted heteroaryl, optionally substituted phenyl; or a pharmaceutically acceptable salt thereof. In some embodiments, R1is alkoxy-substituted phenyl, optionally methoxy- substituted phenyl. In some embodiments, R1is 2-methoxyphenyl. In some embodiments, the compound is selected from KY-2, KY-5, KY-342, KY-6, Imyl-01+, Imate-01; RJG-3017, and RJG-3016. In some embodiments, the compound is RJG- 3017 or RJG-3016. In some embodiments, the presently disclosed subject matter provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound as disclosed herein (e.g., a compound of Formula (I) or (I’)). In some embodiments, the presently disclosed subject matter provides a compound selected from RJG-2096, Tet-02, Tet-03, and Tet-04. In some embodiments, the presently disclosed subject matter provides a method of covalently modifying a peptide or protein, the method comprising: providing a sample comprising a peptide or protein; and contacting the sample with a compound as disclosed herein (e.g., a compound of Formula (I) or (I’)) or a pharmaceutical composition thereof, thereby providing a covalently modified peptide or protein, optionally wherein the covalently modified peptide or protein comprises a covalently modified tyrosine or lysine residue. In some embodiments, the peptide or protein is selected from a glutathione-S-transferase enzyme, Attorney Docket No.: 3062 / 203 PCT optionally glutathione-S-transferase Pi (GSTP1); prostaglandin reductase 2 (PTGR2); aldo- keto reductase family member C1 (AKR1C1); and aldehyde dehydrogenase 3 family member A1 (ALDH3A1). In some embodiments, the presently disclosed subject matter provides a method of inhibiting prostaglandin reductase 2 (PTGR2), wherein the method comprises contacting a sample comprising PTGR2 the with an effective amount of a compound as disclosed herein (e.g., a compound of Formula (I) or (I’)) or a pharmaceutical composition thereof. In some embodiments, the sample comprising PTGR2 is a biological sample selected from a biological fluid, a cell culture, a cell extract, a tissue, a tissue extract, an organ, or an organism. In some embodiments, the compound has a 50% inhibitory concentration (IC50) for PTGR2 of about 25 micromolar or less and / or has reduced off-target effects compared to contacting the sample with a sulfonyl-triazole compound, optionally RJG-2096. In some embodiments, the compound is a compound of Formula (IIb): , wherein G2is selected from the group comprising H, halo, alkyl, substituted alkyl, perhaloalkyl, aralkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; and R1is selected from aryl, heteroaryl, substituted aryl, or substituted heteroaryl, optionally substituted phenyl; or a pharmaceutically acceptable salt thereof. In some embodiments, R1 is alkoxy- substituted phenyl, optionally methoxy-substituted phenyl. In some embodiments, R1is 2- methoxyphenyl. In some embodiments, the compound is RJG-3017 or RJG-3016. In some embodiments, the contacting provides a covalently modified PTGR2, optionally wherein the covalently modified PTGR2 is covalently modified at tyrosine 100 (Y100). In some embodiments, the presently disclosed subject matter provides a method of inhibiting a glutathione-S-transferase enzyme (GST), optionally glutathione-S-transferase Pi (GSTP1), wherein the method comprises contacting a sample comprising the GST with an effective amount of a compound as disclosed herein (e.g., a compound of Formula (I) or (I’)) or a pharmaceutical composition thereof. In some embodiments, the sample comprising the GST is a biological sample selected from a biological fluid, a cell culture, a cell extract, a tissue, Attorney Docket No.: 3062 / 203 PCT a tissue extract, an organ, or an organism. In some embodiments, the compound has a 50% inhibitory concentration (IC50) for GSTP1 of about 5000 nanomolar or less and / or has reduced off-target effects compared to contacting the sample with a sulfonyl-triazole compound, optionally RJG-2096. In some embodiments, the compound is a compound of Formula (IIb): , wherein G2is selected from the group comprising H, halo, alkyl, substituted alkyl, perhaloalkyl, aralkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; and R1 is selected from aryl, heteroaryl, substituted aryl, or substituted heteroaryl, optionally substituted phenyl; or a pharmaceutically acceptable salt thereof. In some embodiments, R1is alkoxy- substituted phenyl, optionally methoxy-substituted phenyl. In some embodiments, R1 is 2- methoxyphenyl. In some embodiments, the compound is RJG-3017 or RJG-3016. In some embodiments, the contacting provides a covalently modified GST, optionally wherein the covalently modified GST comprises a covalently modified tyrosine. Accordingly, it is an object of the presently disclosed subject matter to provide, for example, compounds of Formula (I) and (I’), pharmaceutical compositions, and methods of covalently modifying peptides and proteins, e.g., GSTP1 and PTGR2. This and other objects are achieved in whole or in part by the presently disclosed subject matter. An object of the presently disclosed subject matter having been stated above, other objects and advantages of the presently disclosed subject matter will become apparent to those of ordinary skill in the art after a study of the following description of the presently disclosed subject matter and non-limiting Figures and Examples. BRIEF DESCRIPTION OF THE FIGURES The presently disclosed subject matter will now be described more fully hereinafter with reference to the accompanying Figures, in which representative embodiments are shown. The presently disclosed subject matter can, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the embodiments to those skilled in the art. Certain components in the Attorney Docket No.: 3062 / 203 PCT Figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the presently disclosed subject matter (in some cases schematically). Figures 1A and 1B: Synthesis of sulfonyl-azole (SufAz) probes. General synthetic scheme (Figure 1A) for evaluating the effects of various heterocyclic leaving groups (Py = pyrazole; Imyl = imidazole; Tet = tetrazole) on activity of SufAz probes. (Figure 1B) Sulfonyl- triazole (SuTEx) electrophiles are included for comparison. Figures 2A-2E: Solution reactivity of SufAz probes as determined by HPLC. (Figure 2A) Representative reactions of SufAz probes with nucleophiles that mimic side chain groups of tyrosine (p-cresol) and lysine (n-butylamine). (Figure 2B) Overlay of HPLC chromatograms of SufAz reaction as a function of time. The left arrow denotes the caffeine internal standard. The middle arrow denotes starting material (Imyl-01) and the right arrow denotes the probe- nucleophile product, which was confirmed by a stand-alone injection of a synthetic standard (e.g., the Imyl-01-p-cresol adduct KY-2-48). Plots of probe consumption as a function of time for (Figure 2C) Imyl-01 and amino acid mimetics, (Figure 2D) Imyl-02, Py-02, Tet-02 and HHS-481 reaction with p-cresol, and (Figure 2E) reaction of p-cresol with Imyl probes. Figures 3A-3C: SufAz probe binding activity in lysates and live cells. (Figure 3A) Gel- based chemical proteomic evaluation of SufAz probe labeling of HEK293T soluble proteomes (100 µM, 30 min, 37 ^C). (Figure 3B) Comparison of SufAz probe labeling activity in DM93 soluble and membrane lysate (100 µM, 30 min, 37 ^C). (Figure 3C) Evaluation of SufAz probe labeling in live HEK293T cells (100 µM probe, 2 hr). Each gel is representative of 3 independent replicates. Figures 4A-4E: Imyl probes are tempered tyrosine- and lysine-reactive electrophiles. (Figure 4A) SILAC LC-MS / MS workflow for chemoproteomic profiling of Imyl probes. (Figure 4B) Annotated MS2 spectrum of an Imyl-Br modified tyrosine site (Y100) found in PTGR2. The covalent modification adds 635.2737 Da to the modified amino acid. The data was generated from n = 2-4 independent replicates. (Figure 4C) Comparison of overlapping and distinct probe-modified tyrosine and lysine sites detected by Imyl probes evaluated in cellular labeling studies. (Figure 4D) Evaluation of overlapping and distinct probe-modified sites using Imyl compared with SuTEx probes. (Figure 4E) Chemoselectivity (Y / K ratio) of Imyl compared with SuTEx probes. Squares denote Imyl probes, and the circles denote SuTEx probes. Figures 5A-5C: Evaluating Imyl fragment binding activity by TMT-SuTEx. (Figure 5A) Structures of representative Imyl fragment compounds tested. (Figure 5B) Reactivity of Attorney Docket No.: 3062 / 203 PCT Imyl fragment compounds with tyrosine (p-cresol) and lysine (n-butylamine) side chain group mimetics were compared by HPLC. (Figure 5C) Experimental workflow for detecting protein sites liganded by Imyl fragment compounds (250 µM, 37 ^C, 1 hr) in Colo205 membrane and soluble proteomes as measured by competition of HHS-465 probe labeling. JWB198 (SuTEx fragment) was tested at 25 µM under the same treatment conditions. Additional details on the TMT-SuTEx assay can be found in the EXAMPLES. Peptide isoforms displayed were quantified using Proteome Discoverer to determine site of binding and calculate a competition ratio (CR) for Imyl fragment binding activity. Isoforms denoted in red have a log2CR ratio > 0.5 with a p-value < 0.05. Data are representative of n = 4 biological and technical replicate analyses. Figures 6A-6D: Imidazoles can serve as an effective LG for development of PTGR2 and inhibitors. (Figure 6A) Chemical structures of SuTEx and Imyl-based PTGR2 inhibitors. (Figure 6B) PTGR2 catalyzes the NADPH dependent reduction of 15-keto-PGE2 to 13,14- dihydro-15keto-PGE2. (Figure 6C) LC-MS substrate assay for evaluating PTGR2 activity and inhibition by SuTEx and Imyl inhibitors. Recombinant PTGR2-overexpressed HEK293T lysates were pretreated with compound at the indicated concentrations for 30 min followed by addition of 15-keto-PGE2 substrate. Total lipids were extracted and PTGR2-mediated production of 13,14-dihydro-15-keto-PGE2 were quantified by LC-MS. PTGR2 inhibition was calculated as a %control (inhibitor treatment / vehicle). (Figure 6D) PDAC608T lysates were pretreated with compound then allowed to react with GSH and 1-chloro-3,5-dinitrobenzene (CDNB) to evaluate activity of native GSTs and inhibition by SuTEx and Imyl inhibitors. Inhibition was determined using a % control (inhibitor treatment / vehicle) of the absorbance measured at 340 nm. Figure 7: Nucleophiles mimicking side functional groups of amino acid side chains used for evaluating reactivity of SufAz probes by HPLC. Figure 8: Reaction of SufAz probes with n-butylamine. Data are presented as % consumption of starting material (SufAz probe) signal as detected by HPLC. Data shown are representative of n = 1-3 replicates. Figures 9A and 9B: HPLC assay comparing reactivity of (Figure 9A) Imyl-01+ or (Figure 9B) Imate-01 with nucleophiles in solution. Data shown are representative of n = 2 replicates. Figure 10: Comparing in vitro probe labeling activity of Py-01, Imyl-01m and HHS- 475 in HEK293T, Jurkat, and DM93 soluble and membrane proteomes. Cell lysates were Attorney Docket No.: 3062 / 203 PCT treated with 100 ^M of each respective probe for 2 hours at 37 °C. Gel shown is representative of n = 3 independent replicates. Figure 11: Comparing in vitro probe labeling activity of Imyl compounds in DM93 and HEK293T soluble proteomes. Cell lysates were treated with 100 ^M of each respective probe for 2 hours at 37 °C. Gel shown is representative of n = 3 independent replicates. Figure 12: Time-dependent labeling activity of Imyl-01 in live cells. DM93 cells were treated with 25 ^M Imyl-01 for 10, 20, 30, 60, and 120 min at 37 °C. Gel shown is representative of n = 3 independent replicates. Figure 13: Schematic of TMT-SuTEx for multiplexed evaluation of ligand competition of probe labeling at individual tyrosine and lysine sites by tandem liquid chromatography-mass spectrometry (LC-MS / MS). TMT uses isotopically labeled, amine-reactive reagents that can be multiplexed to yield an isobaric peptide MS1 mass and 2-18 unique MS2 reporter fragment ions (6-plex shown as example and used in the present studies) for simultaneous quantitation by LC-MS / MS. Figures 14A and 14B: (Figure 14A) Probe-modified sites competed by Imyl fragment compound treatment of Colo 205 membrane proteomes as quantified by TMT-SuTEx. Chemical structures of Imyl fragment compounds are shown in each respective volcano plot. (Figure 14B) JWB-198 binding activity in Colo 205 soluble and membrane proteomes as measured by TMT-SuTEx. Sites denoted in red have a log2CR ratio > 0.5 with a p-value < 0.05. Data are representative of n = 4 biological and technical replicate analyses. Figure 15: LC-MS substrate assay for evaluating PTGR2 biochemical activity. Incubation of PTGR2 overexpressing HEK293T lysate with 15-keto-PGE2 substrate resulted in significant production of 13,14-dihydro-15-keto-PGE2 product compared with mock transfected controls. Heat denaturation significantly reduced recombinant PTGR2 activity. ****p <0.0001. DETAILED DESCRIPTION Imidazole-1-sulfonyl and -sulfonate (imidazylate) are widely used in synthetic chemistry as nucleofuges for diazotransfer, nucleophilic substitution, and cross-coupling reactions. The utility of these reagents for protein bioconjugation, in contrast, have not been comprehensively explored and important considering the prevalence of imidazoles in biomolecules and drugs. Disclosed herein is the synthesis of a series of alkyne-modified sulfonyl- and sulfonate-imidazole probes that were used to investigate the utility of this electrophile for protein binding. Alkylation of the distal nitrogen activated the nucleofuge Attorney Docket No.: 3062 / 203 PCT capability of the imidazole to produce sulfonyl-imidazolium electrophiles that were highly reactive but unstable for biological applications. In contrast, arylsulfonyl imidazoles functioned as a tempered electrophile for assessing ligandability of select tyrosine and lysine sites in cell proteomes and when mated to a recognition element could produce targeted covalent inhibitors with reduced off-target activity. In summary, imidazole nucleofuges showed balanced stability and tunability to produce sulfone-based electrophiles that bind functional tyrosine and lysine sites in the proteome. The presently disclosed subject matter will now be described more fully hereinafter with reference to the accompanying Figures and EXAMPLES, in which representative embodiments are shown. The presently disclosed subject matter can, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the embodiments to those skilled in the art. Certain components in the Figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the presently disclosed subject matter (in some cases schematically). Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the presently described subject matter belongs. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. Throughout the specification and claims, a given chemical formula or name shall encompass all active optical and stereoisomers, as well as racemic mixtures where such isomers and mixtures exist. I. Definitions The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the presently disclosed subject matter. While the following terms are believed to be well understood by one of ordinary skill in the art, the following definitions are set forth to facilitate explanation of the presently disclosed subject matter. Following long-standing patent law convention, the terms “a”, “an”, and “the” refer to “one or more” when used in this application, including in the claims. For example, the phrase “a protein” refers to one or more proteins, including a plurality of the same protein. Similarly, the phrase “at least one”, when employed herein to refer to an entity, refers to, for example, 1, Attorney Docket No.: 3062 / 203 PCT 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, or more of that entity, including but not limited to whole number values between 1 and 100 and greater than 100. Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about”. The term “about”, as used herein when referring to a measurable value such as an amount of mass, weight, time, volume, concentration, or percentage, is meant to encompass variations of in some embodiments ±20%, in some embodiments ±10%, in some embodiments ±5%, in some embodiments ±1%, in some embodiments ±0.5%, and in some embodiments ±0.1 % from the specified amount, as such variations are appropriate to perform the disclosed methods and / or employ the disclosed compositions. Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by the presently disclosed subject matter. As used herein, the term “and / or” when used in the context of a list of entities, refers to the entities being present singly or in combination. Thus, for example, the phrase “A, B, C, and / or D” includes A, B, C, and D individually, but also includes any and all combinations and subcombinations of A, B, C, and D. The term “comprising”, which is synonymous with “including” “containing”, or “characterized by”, is inclusive or open-ended and does not exclude additional, unrecited elements and / or method steps. “Comprising” is a term of art that means that the named elements and / or steps are present, but that other elements and / or steps can be added and still fall within the scope of the relevant subject matter. As used herein, the phrase “consisting essentially of” limits the scope of the related disclosure or claim to the specified materials and / or steps, plus those that do not materially affect the basic and novel characteristic(s) of the disclosed and / or claimed subject matter. For example, a pharmaceutical composition can “consist essentially of” a pharmaceutically active agent or a plurality of pharmaceutically active agents, which means that the recited pharmaceutically active agent(s) is / are the only pharmaceutically active agent(s) present in the pharmaceutical composition. It is noted, however, that carriers, excipients, and / or other inactive agents can and likely would be present in such a pharmaceutical composition and are encompassed within the nature of the phrase “consisting essentially of”. As used herein, the phrase “consisting of” excludes any element, step, or ingredient not specifically recited. It is noted that, when the phrase “consists of” appears in a clause of the Attorney Docket No.: 3062 / 203 PCT body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole. With respect to the terms “comprising”, “consisting of”, and “consisting essentially of”, where one of these three terms is used herein, the presently disclosed and claimed subject matter can include the use of either of the other two terms. For example, a composition that in some embodiments comprises a given active agent also in some embodiments can consist essentially of that same active agent, and indeed can in some embodiments consist of that same active agent. The terms “additional therapeutically active compound” and “additional therapeutic agent”, as used in the context of the presently disclosed subject matter, refers to the use or administration of a compound for an additional therapeutic use for a particular injury, disease, or disorder being treated. Such a compound, for example, could include one being used to treat an unrelated disease or disorder, or a disease or disorder which may not be responsive to the primary treatment for the injury, disease, or disorder being treated. As used herein, the terms “administration of” and / or “administering” a compound should be understood to refer to providing a compound of the presently disclosed subject matter to a subject in need of treatment. The term “aqueous solution” as used herein can include other ingredients commonly used, such as sodium bicarbonate described herein, and further includes any acid or base solution used to adjust the pH of the aqueous solution while solubilizing a peptide. The term “binding” refers to the adherence of molecules to one another, such as, but not limited to, enzymes to substrates, ligands to receptors, antibodies to antigens, DNA binding domains of proteins to DNA, and DNA or RNA strands to complementary strands. “Binding partner”, as used herein, refers to a molecule capable of binding to another molecule. The term “biocompatible”, as used herein, refers to a material that does not elicit a substantial detrimental response in the host. As used herein, the terms “biologically active fragment” and “bioactive fragment” of a peptide encompass natural and synthetic portions of a longer peptide or protein that are capable of specific binding to their natural ligand and / or of performing a desired function of a protein, for example, a fragment of a protein of larger peptide which still contains the epitope of interest and is immunogenic. Attorney Docket No.: 3062 / 203 PCT The term “biological sample”, as used herein, refers to samples obtained from a subject, including but not limited to skin, hair, tissue, blood, plasma, cells, sweat, and urine. A “control” cell, tissue, sample, or subject is a cell, tissue, sample, or subject of the same type as a test cell, tissue, sample, or subject. The control may, for example, be examined at precisely or nearly the same time the test cell, tissue, sample, or subject is examined. The control may also, for example, be examined at a time distant from the time at which the test cell, tissue, sample, or subject is examined, and the results of the examination of the control may be recorded so that the recorded results may be compared with results obtained by examination of a test cell, tissue, sample, or subject. The control may also be obtained from another source or similar source other than the test group or a test subject, where the test sample is obtained from a subject suspected of having a condition, disease, or disorder for which the test is being performed. A “test” cell is a cell being examined. A “pathogenic” cell is a cell that, when present in a tissue, causes or contributes to a condition, disease, or disorder in the animal in which the tissue is located (or from which the tissue was obtained). A tissue “normally comprises” a cell if one or more of the cell are present in the tissue in an animal not afflicted with a condition, disease, or disorder. As used herein, the terms “condition”, “disease condition”, “disease”, “disease state”, and “disorder” refer to physiological states in which diseased cells or cells of interest can be targeted with the compositions of the presently disclosed subject matter. As used herein, the term “diagnosis” refers to detecting a risk or propensity to a condition, disease, or disorder. In any method of diagnosis exist false positives and false negatives. Any one method of diagnosis does not provide 100% accuracy. A “disease” is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal’s health continues to deteriorate. In contrast, a “disorder” in an animal is a state of health in which the animal is able to maintain homeostasis, but in which the animal’s state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal’s state of health. As used herein, an “effective amount” or “therapeutically effective amount” refers to an amount of a compound or composition sufficient to produce a selected effect, such as but Attorney Docket No.: 3062 / 203 PCT not limited to alleviating symptoms of a condition, disease, or disorder. In the context of administering compounds in the form of a combination, such as multiple compounds, the amount of each compound, when administered in combination with one or more other compounds, may be different from when that compound is administered alone. Thus, an effective amount of a combination of compounds refers collectively to the combination as a whole, although the actual amounts of each compound may vary. The term “more effective” means that the selected effect occurs to a greater extent by one treatment relative to the second treatment to which it is being compared. As used herein, an “essentially pure” preparation of a particular protein or peptide is a preparation wherein in some embodiments at least about 95% and in some embodiments at least about 99%, by weight, of the protein or peptide in the preparation is the particular protein or peptide. In some embodiments, the terms “fragment”, “segment”, or “subsequence” as used herein refers to a portion of an amino acid sequence, comprising at least one amino acid, or a portion of a nucleic acid sequence comprising at least one nucleotide. Thus, in some embodiments, the terms “fragment”, “segment”, and “subsequence” are used interchangeably herein. The term “sulfonyl-azole compound” (or “SufAz compound”) as used herein refers to a synthetic compound that includes a sulfonyl group directly attached to a nitrogen atom of an azole ring (e.g., an imidazole (Imyl) ring). The azole moiety can be substituted or unsubstituted. Typically, a SufAz compound can undergo a covalent reaction with a nucleophilic group in which the sulfonyl group of SufAz compound acts as an electrophile and the azole moiety can act as a leaving group. As used herein, the term “probe” (as in “covalent probe” or “sulfonyl-azole (SufAz) probe”) can refer to a small molecule comprising an electrophile (e.g., a sulfonyl electrophile) that is broadly reactive and can be used to detect sites amenable to covalent reactions. Probes can include a tag for detection. The tag for detection can be a moiety that can be directly used for detection (e.g., a fluorophore, biotin or another affinity label, a radioisotope, etc.) or a moiety (e.g., an alkyne group) that can be chemically modified to incorporate a detectable group (e.g., biotin) after the probe has undergone a covalent reaction with a probe reactive site. In contrast, the term “ligand” (as in “covalent ligand” or “SufAz ligand”) can refer to a synthetic small molecule compound that includes an electrophile and that does not include a tag for detection and / or that has been tailored to undergo covalent reactions more selectively Attorney Docket No.: 3062 / 203 PCT with a particular reactive site and / or protein and / or peptide of interest. For example, the selectivity of a SufAz ligand can be tailored via the addition of substituents that can alter the reactivity of the compound via steric or electronic effects. In some embodiments, the ligands can be used for the development of therapeutic agents that target and / or modulate the activity of one or more particular biological molecules of interest. Thus, as used herein, in some embodiments, “ligand” can refer to a synthetic molecule (e.g., a SufAz compound) that binds to a target compound or molecule, such as a reactive nucleophilic amino acid residue in a peptide or protein. In some embodiments, as can be determined by one of ordinary skill in the art based on context, the term “ligand” as used herein can be used more generally to refer to any entity (e.g., a molecule) that specifically or selectively binds to or is specifically or selectively reactive with a second entity (e.g., a biomolecule, such as a peptide, protein, nucleic acid, lipid, etc.) when the ligand functions in a binding reaction which is determinative of the presence of the second entity in a heterogenous sample (i.e., a sample comprising a plurality of different entities, such as a plurality of different biomolecules). As used herein, a “functional” biological molecule is a biological molecule in a form in which it exhibits a property by which it can be characterized. A functional enzyme, for example, is one that exhibits the characteristic catalytic activity by which the enzyme can be characterized. As used herein “injecting”, “applying”, and administering” include administration of a compound of the presently disclosed subject matter by any number of routes and modes including, but not limited to, topical, oral, buccal, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual, vaginal, ophthalmic, pulmonary, vaginal, and rectal approaches. As used herein, the term “linkage” refers to a connection between two groups. The connection can be either covalent or non-covalent, including but not limited to ionic bonds, hydrogen bonding, and hydrophobic / hydrophilic interactions. As used herein, the term “linker” refers to a molecule that joins two other molecules either covalently or noncovalently, such as but not limited to through ionic or hydrogen bonds or van der Waals interactions. The terms “measuring the level of expression” and “determining the level of expression” as used herein refer to any measure or assay which can be used to correlate the Attorney Docket No.: 3062 / 203 PCT results of the assay with the level of expression of a gene or protein of interest. Such assays include measuring the level of mRNA, protein levels, etc. and can be performed by assays such as northern and western blot analyses, binding assays, immunoblots, etc. The level of expression can include rates of expression and can be measured in terms of the actual amount of an mRNA or protein present. Such assays are coupled with processes or systems to store and process information and to help quantify levels, signals, etc. and to digitize the information for use in comparing levels. The term “otherwise identical sample”, as used herein, refers to a sample similar to a first sample, that is, it is obtained in the same manner from the same subject from the same tissue or fluid, or it refers a similar sample obtained from a different subject. The term “otherwise identical sample from an unaffected subject” refers to a sample obtained from a subject not known to have the disease or disorder being examined. The sample may of course be a standard sample. By analogy, the term “otherwise identical” can also be used regarding regions or tissues in a subject or in an unaffected subject. As used herein, “parenteral administration” of a pharmaceutical composition includes any route of administration characterized by physical breaching of a tissue of a subject and administration of the pharmaceutical composition through the breach in the tissue. Parenteral administration thus includes, but is not limited to, administration of a pharmaceutical composition by injection of the composition, by application of the composition through a surgical incision, by application of the composition through a tissue-penetrating non-surgical wound, and the like. In particular, parenteral administration is contemplated to include, but is not limited to, subcutaneous, intraperitoneal, intramuscular, intrasternal injection, and kidney dialytic infusion techniques. The term “pharmaceutical composition” refers to a composition comprising at least one active ingredient, whereby the composition is amenable to investigation for a specified, efficacious outcome in a mammal (for example, without limitation, a human). Those of ordinary skill in the art will understand and appreciate the techniques appropriate for determining whether an active ingredient has a desired efficacious outcome based upon the needs of the artisan. “Pharmaceutically acceptable” means physiologically tolerable, for either human or veterinary application. Similarly, “pharmaceutical compositions” include formulations for human and veterinary use. Attorney Docket No.: 3062 / 203 PCT As used herein, the term “pharmaceutically acceptable carrier” means a chemical composition with which an appropriate compound or derivative can be combined and which, following the combination, can be used to administer the appropriate compound to a subject. As used herein, the term “physiologically acceptable” ester or salt means an ester or salt form of the active ingredient which is compatible with any other ingredients of the pharmaceutical composition, which is not deleterious to the subject to which the composition is to be administered. “Plurality” means at least two. As used herein, the term “mass spectrometry” (MS) refers to a technique for the identification and / or quantitation of molecules in a sample. MS includes ionizing the molecules in a sample, forming charged molecules; separating the charged molecules according to their mass-to-charge ratio; and detecting the charged molecules. MS allows for both the qualitative and quantitative detection of molecules in a sample. The molecules can be ionized and detected by any suitable means known to one of skill in the art. Some examples of mass spectrometry are “tandem mass spectrometry” or “MS / MS,” which are the techniques wherein multiple rounds of mass spectrometry occur, either simultaneously using more than one mass analyzer or sequentially using a single mass analyzer. The term “mass spectrometry” can refer to the application of mass spectrometry to protein analysis. In some embodiments, electrospray ionization (ESI) and matrix-assisted laser desorption / ionization (MALDI) can be used in this context. In some embodiments, intact protein molecules can be ionized by the above techniques, and then introduced to a mass analyzer. Alternatively, protein molecules can be broken down into smaller peptides, for example, by enzymatic digestion by a protease, such as trypsin. Subsequently, the peptides are introduced into the mass spectrometer and identified by peptide mass fingerprinting or tandem mass spectrometry. As used herein, the term “mass spectrometer” is used to refer an apparatus for performing mass spectrometry that includes a component for ionizing molecules and detecting charged molecules. Various types of mass spectrometers can be employed in the methods of the presently disclosed subject matter. For example, whole protein mass spectroscopy analysis can be conducted using time-of-flight (TOF) or Fourier transform ion cyclotron resonance (FT- ICR) instruments. For peptide mass analysis, MALDI time-of-flight instruments can be employed, as they permit the acquisition of peptide mass fingerprints (PMFs) at high pace. Multiple stage quadrupole-time-of-flight and the quadrupole ion trap instruments can also be used. Attorney Docket No.: 3062 / 203 PCT The terms “high throughput protein identification,” “proteomics” and other related terms are used herein to refer to the processes of identification of a large number or (in some cases, all) proteins in a certain protein complement. Post-translational protein modifications and quantitative information can also be assessed by such methods. One example of “high throughput protein identification” is a gel-based process that includes the pre-fractionation and purification of proteins by one-dimensional protein gel electrophoresis. The gel can then be fractionated into several molecular weight fractions to reduce sample complexity, and proteins can be in-gel digested with trypsin. The tryptic peptides are extracted from the gel, further fractionated by liquid chromatography, and analyzed by mass spectrometry. In another approach, a sample can be fractionated without using the gels, for example, by protein extraction followed by liquid chromatography. The proteins can then be digested in-solution, and the proteolytic fragments further fractionated by liquid chromatography and analyzed by mass spectrometry. As used herein, the term “Western blot,” which can be also referred to as “immunoblot”, and related terms refer to an analytical technique used to detect specific proteins in a sample. The technique uses gel electrophoresis to separate the proteins, which are then transferred from the gel to a membrane (typically nitrocellulose or PVDF) and stained, in membrane, with antibodies specific to the target protein. The expression “stable isotope labeling by amino acids in cell culture” (SILAC) is used herein to refer to an approach for incorporation of a label into proteins for mass spectrometry (MS)-based quantitative proteomics. SILAC comprises metabolic incorporation of a given “light” or “heavy” form of the amino acid into the proteins. For example, SILAC comprises the incorporation of amino acids with substituted stable isotopic nuclei (e.g., deuterium,13C,15N). In an illustrative SILAC experiment, two cell populations are grown in culture media that are identical, except that one of them contains a “light” and the other a “heavy” form of a particular amino acid (for example,12C and13C labeled L-lysine, respectively). When the labeled analog of an amino acid is supplied to cells in culture instead of the natural amino acid, it is incorporated into all newly synthesized proteins. After a number of cell divisions, each instance of the amino acid is replaced by its isotope-labeled analog. Since there is little chemical difference between the labeled amino acid and the natural amino acid isotopes, the cells behave substantially similar to the control cell population grown in the presence of a normal amino acid. Attorney Docket No.: 3062 / 203 PCT The term “prevent” as used herein means to stop something from happening, or taking advance measures against something possible or probable from happening. In the context of medicine, “prevention” generally refers to action taken to decrease the chance of getting a disease or condition. It is noted that “prevention” need not be absolute, and thus can occur as a matter of degree. A “preventive” or “prophylactic” treatment is a treatment administered to a subject who does not exhibit signs, or exhibits only early signs, of a condition, disease, or disorder. A prophylactic or preventative treatment is administered for the purpose of decreasing the risk of developing pathology associated with developing the condition, disease, or disorder. “Polypeptide” refers to a polymer composed of amino acid residues, related naturally occurring structural variants, and synthetic non-naturally occurring analogs thereof linked via peptide bonds, related naturally occurring structural variants, and synthetic non-naturally occurring analogs thereof. “Synthetic peptides or polypeptides” refers to non-naturally occurring peptides or polypeptides. Synthetic peptides or polypeptides can be synthesized, for example, using an automated polypeptide synthesizer. Various solid phase peptide synthesis methods are known to those of skill in the art. The term “protein” typically refers to large polypeptides (e.g., greater than 50 amino acid residues). Conventional notation is used herein to portray polypeptide sequences: the left- hand end of a polypeptide sequence is the amino-terminus; the right-hand end of a polypeptide sequence is the carboxyl-terminus. As used herein, the term “peptide” refers to a smaller polypeptide, e.g., having 2 to about 50 amino acid residues (e.g., about 5 to 50 amino acid or 10 to 50 amino acid residues). The term “amino acid residue” refers to a moiety resulting from the incorporation of an amino acid into a polypeptide, e.g., a moiety having the structure -NH-CH(R)-C(=O)-, where R corresponds to the side chain of the amino acid from which the residue originates. The term “proteome” refers to the entire set of proteins expressed by a genome, cell, tissue, or organism at a particular time and / or under particular conditions. As used herein, the term “purified” and like terms relate to an enrichment of a molecule or compound relative to other components normally associated with the molecule or compound in a native environment. The term “purified” does not necessarily indicate that complete purity of the particular molecule has been achieved during the process. Attorney Docket No.: 3062 / 203 PCT A “highly purified” compound as used herein refers to a compound that is in some embodiments greater than 90% pure, that is in some embodiments greater than 95% pure, and that is in some embodiments greater than 98% pure. As used herein, the term “mammal” refers to any member of the class Mammalia, including, without limitation, humans, and nonhuman primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, sheep, pigs, goats, and horses; domestic mammals such as dogs and cats; laboratory animals including rodents such as mice, rats and guinea pigs, and the like. The term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be included within the scope of this term. The term “subject” as used herein refers to a member of species for which treatment and / or prevention of a disease or disorder using the compositions and methods of the presently disclosed subject matter might be desirable. Accordingly, the term “subject” is intended to encompass in some embodiments any member of the Kingdom Animalia including, but not limited to the phylum Chordata (e.g., members of Classes Osteichthyes (bony fish), Amphibia (amphibians), Reptilia (reptiles), Aves (birds), and Mammalia (mammals), and all Orders and Families encompassed therein. The compositions and methods of the presently disclosed subject matter are particularly useful for warm-blooded vertebrates. Thus, in some embodiments the presently disclosed subject matter concerns mammals and birds. More particularly provided are compositions and methods derived from and / or for use in mammals such as humans and other primates, as well as those mammals of importance due to being endangered (such as Siberian tigers), of economic importance (animals raised on farms for consumption by humans) and / or social importance (animals kept as pets or in zoos) to humans, for instance, carnivores other than humans (such as cats and dogs), swine (pigs, hogs, and wild boars), ruminants (such as cattle, oxen, sheep, giraffes, deer, goats, bison, and camels), rodents (such as mice, rats, and rabbits), marsupials, and horses. Also provided is the use of the disclosed methods and compositions on birds, including those kinds of birds that are endangered, kept in zoos, as well as fowl, and more particularly domesticated fowl, e.g., poultry, such as turkeys, chickens, ducks, geese, guinea fowl, and the like, as they are also of economic importance to humans. Thus, also provided is the use of the disclosed methods and compositions on livestock, including but not limited to domesticated swine (pigs and hogs), ruminants, horses, poultry, and the like. Attorney Docket No.: 3062 / 203 PCT A “sample”, as used herein, refers in some embodiments to a biological sample from a subject, including, but not limited to, normal tissue samples, diseased tissue samples, biopsies, blood, saliva, feces, semen, tears, and urine. A sample can also be any other source of material obtained from a subject which contains proteins, cells, tissues, or fluid of interest. A sample can also be obtained from cell or tissue culture. The term “standard”, as used herein, refers to something used for comparison. For example, it can be a known standard agent or compound which is administered and used for comparing results when administering a test compound, or it can be a standard parameter or function which is measured to obtain a control value when measuring an effect of an agent or compound on a parameter or function. Standard can also refer to an “internal standard”, such as an agent or compound which is added at known amounts to a sample and is useful in determining such things as purification or recovery rates when a sample is processed or subjected to purification or extraction procedures before a marker of interest is measured. Internal standards are often a purified marker of interest which has been labeled, such as with a radioactive isotope, allowing it to be distinguished from an endogenous marker. A “subject” of analysis, diagnosis, or treatment is an animal. Such animals include mammals, in some embodiments, humans. As used herein, a “subject in need thereof” is a patient, animal, mammal, or human, who will benefit from the method of this presently disclosed subject matter. The term “substantially pure” describes a compound, e.g., a protein or polypeptide, which has been separated from components which naturally accompany it. Typically, a compound is substantially pure when in some embodiments at least 10%, in some embodiments at least 20%, in some embodiments at least 50%, in some embodiments at least 60%, in some embodiments at least 75%, in some embodiments at least 90%, and in some embodiments at least 99% of the total material (by volume, by wet or dry weight, or by mole percent or mole fraction) in a sample is the compound of interest. Purity can be measured by any appropriate method, e.g., in the case of polypeptides by column chromatography, gel electrophoresis, or HPLC analysis. A compound, e.g., a protein, is also substantially purified when it is essentially free of naturally associated components or when it is separated from the native contaminants which accompany it in its natural state. The term “symptom”, as used herein, refers to any morbid phenomenon or departure from the normal in structure, function, or sensation, experienced by the patient and indicative Attorney Docket No.: 3062 / 203 PCT of disease. In contrast, a “sign” is objective evidence of disease. For example, a bloody nose is a sign. It is evident to the patient, doctor, nurse, and other observers. A “therapeutic” treatment is a treatment administered to a subject who exhibits signs of pathology for the purpose of diminishing or eliminating those signs. A “therapeutically effective amount” of a compound is that amount of compound which is sufficient to provide a beneficial effect to the subject to which the compound is administered. As used herein, the phrase “therapeutic agent” refers to an agent that is used to, for example, treat, inhibit, prevent, mitigate the effects of, reduce the severity of, reduce the likelihood of developing, slow the progression of, and / or cure, a disease or disorder. The terms “treatment” and “treating” as used herein refer to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) the targeted pathologic condition, prevent the pathologic condition, pursue or obtain beneficial results, and / or lower the chances of the individual developing a condition, disease, or disorder, even if the treatment is ultimately unsuccessful. Those in need of treatment include those already with the condition as well as those prone to have or predisposed to having a condition, disease, or disorder, or those in whom the condition is to be prevented. All genes, gene names, and gene products disclosed herein are intended to correspond to homologs and / or orthologs from any species for which the compositions and methods disclosed herein are applicable. Thus, the terms include, but are not limited to genes and gene products from humans and mice. It is understood that when a gene or gene product from a particular species is disclosed, this disclosure is intended to be exemplary only, and is not to be interpreted as a limitation unless the context in which it appears clearly indicates. As used herein, the term “AKR1C1” refers to the aldo-keto reductase family 1 member C1 gene and its transcription and translation products. Exemplary human AKR1C1 nucleic acid and amino acid sequences are presented in Accession Nos. NM_001353.6 and NP_001344.2 of the GENBANK® biosequence database. As used herein, the term “ALDH3A1” refers to the aldehyde dehydrogenase 3 family member A1 gene and its transcription and translation products. Exemplary human ALDH3A1 nucleic acid and amino acid sequences are presented in Accession Nos. NM_000691.5 and NP_000682.3 of the GENBANK® biosequence database. As used herein, the term “GSTP1” refers to the glutathione S-transferase pi 1 gene and its transcription and translation products. Exemplary human GSTP1 nucleic acid and amino Attorney Docket No.: 3062 / 203 PCT acid sequences are presented in Accession Nos. NM_000852.4 and NP_000843.1 of the GENBANK® biosequence database. As used herein, the term “PTGR2” refers to the prostaglandin reductase 2 gene and its transcription and translation products. Exemplary human PTGR2 nucleic acid and amino acid sequences are presented in Accession Nos. NM_001146154.2 and NP_001139626.1 of the GENBANK® biosequence database. As used herein the term “alkyl” refers to C1-20inclusive, linear (i.e., “straight-chain”), branched, or cyclic, saturated or at least partially and in some cases fully unsaturated (i.e., alkenyl and alkynyl) hydrocarbon chains, including for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, octyl, ethenyl, propenyl, butenyl, pentenyl, hexenyl, octenyl, butadienyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, and allenyl groups. “Branched” refers to an alkyl group in which a lower alkyl group, such as methyl, ethyl or propyl, is attached to a linear alkyl chain. In some embodiments, the alkyl group is “lower alkyl.” “Lower alkyl” refers to an alkyl group having 1 to about 8 carbon atoms (i.e., a C1-8 alkyl), e.g., 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms. In some embodiments, the alkyl is “higher alkyl.” “Higher alkyl” refers to an alkyl group having about 10 to about 20 carbon atoms, e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms. In certain embodiments, “alkyl” refers, in particular, to C1-8 straight-chain alkyls. In other embodiments, “alkyl” refers, in particular, to C1-8branched-chain alkyls. Alkyl groups can optionally be substituted (a “substituted alkyl”) with one or more alkyl group substituents, which can be the same or different. The term “alkyl group substituent” includes but is not limited to alkyl, substituted alkyl, halo, arylamino, acyl, hydroxyl, aryloxyl, alkoxyl, alkylthio, arylthio, aralkyloxyl, aralkylthio, carboxyl, alkoxycarbonyl, oxo, and cycloalkyl. There can be optionally inserted along the alkyl chain one or more oxygen, sulfur or substituted or unsubstituted nitrogen atoms, wherein the nitrogen substituent is hydrogen, lower alkyl (also referred to herein as “alkylaminoalkyl”), or aryl. Thus, as used herein, the term “substituted alkyl” includes alkyl groups, as defined herein, in which one or more atoms or functional groups of the alkyl group are replaced with another atom or functional group, including for example, alkyl, substituted alkyl, halogen, aryl, substituted aryl, alkoxyl, hydroxyl, nitro, amino, alkylamino, dialkylamino, sulfate, and mercapto. The term “aryl” is used herein to refer to an aromatic moiety that can be a single aromatic ring, or multiple aromatic rings that are fused together, linked covalently, or linked to Attorney Docket No.: 3062 / 203 PCT a common group, such as, but not limited to, a methylene or ethylene moiety. The common linking group also can be a carbonyl, as in benzophenone, or oxygen, as in diphenylether, or nitrogen, as in diphenylamine. The term “aryl” specifically encompasses heterocyclic aromatic compounds. The aromatic ring(s) can comprise phenyl, naphthyl, biphenyl, diphenylether, diphenylamine and benzophenone, among others. In particular embodiments, the term “aryl” means a cyclic aromatic comprising about 5 to about 10 carbon atoms, e.g., 5, 6, 7, 8, 9, or 10 carbon atoms, and including 5- and 6-membered hydrocarbon and heterocyclic aromatic rings. The aryl group can be optionally substituted (a “substituted aryl”) with one or more aryl group substituents, which can be the same or different, wherein “aryl group substituent” includes alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, hydroxyl, alkoxyl, aryloxyl, aralkyloxyl, carboxyl, carbonyl, acyl, halo, nitro, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, acyloxyl, acylamino, aroylamino, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, arylthio, alkylthio, alkylene, and -NR’R’’, wherein R’ and R’’ can each be independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, and aralkyl. Thus, as used herein, the term “substituted aryl” includes aryl groups, as defined herein, in which one or more atoms or functional groups of the aryl group are replaced with another atom or functional group, including for example, alkyl, substituted alkyl, halogen, aryl, substituted aryl, alkoxyl, hydroxyl, nitro, amino, alkylamino, dialkylamino, sulfate, and mercapto. Specific examples of aryl groups include, but are not limited to, cyclopentadienyl, phenyl, furan, thiophene, pyrrole, pyran, pyridine, imidazole, benzimidazole, isothiazole, isoxazole, pyrazole, pyrazine, triazine, pyrimidine, quinoline, isoquinoline, indole, carbazole, and the like. The term “heteroaryl” refers to aryl groups wherein at least one atom of the backbone of the aromatic ring or rings is an atom other than carbon. Thus, heteroaryl groups have one or more non-carbon atoms selected from the group including, but not limited to, nitrogen, oxygen, and sulfur. As used herein, the term “acyl” refers to an organic carboxylic acid group wherein the -OH of the carboxyl group has been replaced with another substituent, i.e., as represented by -C(=O)R, wherein R is an alkyl, substituted alkyl, aralkyl, substituted aralkyl, aryl or substituted aryl group as defined herein). As such, the term “acyl” specifically includes arylacyl groups, such as an acetylfuran and a phenacyl group. Specific examples of acyl groups include acetyl and benzoyl. Attorney Docket No.: 3062 / 203 PCT “Cyclic” and “cycloalkyl” refer to a non-aromatic mono- or multicyclic ring system of about 3 to about 10 carbon atoms, e.g., 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms. The cycloalkyl group can be optionally partially unsaturated. The cycloalkyl group also can be optionally substituted with an alkyl group substituent as defined herein, oxo, and / or alkylene. There can be optionally inserted along the cyclic alkyl chain one or more oxygen, sulfur or substituted or unsubstituted nitrogen atoms, wherein the nitrogen substituent is hydrogen, alkyl, substituted alkyl, aryl, or substituted aryl, thus providing a heterocyclic group. Representative monocyclic cycloalkyl rings include cyclopentyl, cyclohexyl, and cycloheptyl. Multicyclic cycloalkyl rings include adamantyl, octahydronaphthyl, decalin, camphor, camphane, and noradamantyl. The terms “heterocycle”, “heterocyclyl” “heterocycloalkyl” or “heterocyclic” refer to cycloalkyl groups (i.e., non-aromatic, cyclic groups as described hereinabove) wherein one or more of the backbone carbon atoms of a cyclic ring is replaced by a heteroatom (e.g., nitrogen, sulfur, or oxygen). Examples of heterocycles include, but are not limited to, tetrahydrofuran, tetrahydropyran, morpholine, dioxane, piperidine, piperazine, and pyrrolidine. Additional examples of heterocycles include, for example, the cyclic forms of sugars, such as ribose, glucose, galactose, and the like. “Alkylene” refers to a straight or branched bivalent aliphatic hydrocarbon group having from 1 to about 20 carbon atoms, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms. The alkylene group can be straight, branched or cyclic. The alkylene group also can be optionally unsaturated and / or substituted with one or more “alkyl group substituents.” There can be optionally inserted along the alkylene group one or more oxygen, sulfur or substituted or unsubstituted nitrogen atoms (also referred to herein as “alkylaminoalkyl”), wherein the nitrogen substituent is alkyl as previously described. Exemplary alkylene groups include methylene (-CH2-); ethylene (-CH2-CH2-); propylene (- (CH2)3-); cyclohexylene (-C6H10-); -CH=CH—CH=CH-; -CH=CH-CH2-; -(CH2)q-N(R)- (CH2)r-, wherein each of q and r is independently an integer from 0 to about 20, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, and R is hydrogen or lower alkyl; methylenedioxyl (-O-CH2-O-); and ethylenedioxyl (-O-(CH2)2-O-). An alkylene group can have about 2 to about 3 carbon atoms and can further have 6-20 carbons. “Alkoxyl” or “alkoxy” refers to an alkyl-O- group wherein alkyl is as previously described. The term “alkoxyl” as used herein can refer to, for example, methoxyl, ethoxyl, propoxyl, isopropoxyl, butoxyl, t-butoxyl, and pentoxyl. The term “oxyalkyl” can be used interchangably with “alkoxyl”. Attorney Docket No.: 3062 / 203 PCT The terms “aryloxy” and “aryloxyl” refer to an aryl-O-group, wherein aryl is as previously described. The term “aryloxy as used herein can refer to, for example, phenoxy, p- chlorophenoxy, p-fluorophenoxy, p-methylphenoxy, p-methoxyphenoxy, and the like. “Aralkyl” refers to an aryl-alkyl- group wherein aryl and alkyl are as previously described and include substituted aryl and substituted alkyl. Exemplary aralkyl groups include benzyl, phenylethyl, and naphthylmethyl. In some embodiments, the aromatic portion of the aralkyl group can be substituted by one or more aryl group substituents and / or the alkyl portion of the aralkyl group can be substituted by one or more alkyl group substituents and the aralkyl group can be a “substituted aralkyl” group. The term “amino” refers to the -NR’R” group, wherein R’ and R” are each independently selected from the group including H and substituted and unsubstituted alkyl, cycloalkyl, heterocycle, aralkyl, aryl, and heteroaryl. In some embodiments, the amino group is -NH2. The terms “alkylamino” and “aminoalkyl” refer to a -NHR group where R is alkyl or substituted alkyl. The term “arylamino” refers to a -NHR group where R is aryl or substituted aryl. The term “carbonyl” refers to the -(C=O)- or a double bonded oxygen substituent attached to a carbon atom of a previously named parent group. The terms “carboxylate” and “carboxylic acid” can refer to the groups -C(=O)-O- and - C(=O)-OH, respectively. In some embodiments, “carboxylate” can refer to either the -C(=O)- O- or -C(=O)-OH group. In some embodiments, the term “carboxyl” can also be used to refer to a carboxylate or carboxylic acid group. The terms “sulfonyl” as used herein refers to the -S(=O)2- or -S(=O)2R group, wherein R is alkyl, substituted alkyl, cycloalkyl, heterocycloalkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl. The term “sulfonamide” refers to the -S(=O)2-N(R)2group, wherein each R is independently selected from H, alkyl, substituted alkyl, aralkyl, substituted aralkyl, aryl, and substituted aryl, or wherein the two R together can form a ring with the nitrogen atom (e.g., wherein the two R together are an alkylene group, such as a butylene or pentylene group). The term “sulfonate” as used herein refers to a -S(=O)2-O-R group, wherein R is selected from alkyl, substituted alkyl, aralkyl, substituted aralkyl, aryl, and substituted aryl. The terms “halo”, “halide”, or “halogen” as used herein refer to fluoro, chloro, bromo, and iodo groups. Attorney Docket No.: 3062 / 203 PCT The term “perhaloalkyl” refers to an alkyl group wherein all of the hydrogen atoms are replaced by halo. Thus, for example, perhaloalkyl can refer to a “perfluroalkyl” group wherein all of the hydrogen atoms of the alkyl group are replaced by fluoro. Perhaloalkyl groups include, but are not limited to, -CF3. The terms “hydroxyl” and “hydroxy” refer to the -OH group. The term “oxo” refers to a compound described previously herein wherein a carbon atom is replaced by an oxygen atom. The term “thio” refers to the -S- or -SH group. The terms “alkylthio” and “thioalkyl” refer to a -SR group where R is alkyl or substituted alkyl. The term “arylthiol” refers to a -SR group where R is aryl or substituted aryl. The term “cyano” refers to the -CN group. The term “nitro” refers to the -NO2 group. A line crossed by a wavy line, e.g., in the structure: indicates the site where the indicated substituent or structure can bond to another group. II. Compositions II.A. Introduction Imidazole is a five-membered nitrogen heterocycle that has found widespread use in organic chemistry because of its distinct chemical properties (e.g., aromaticity and basicity). When attached to sulfonyl and sulfonate groups at the N1 position, the resulting sulfonyl- and sulfonate-imidazole (also referred to as imidazylates), and activated analogs (N3 methylated imidazoles; see U.S. Patent No. 11,680,060), can serve as effective nucleofuges in various functional group transformations (Fevig et al., 1988; Massa et al., 1992; Goddard-Borger & Stick, 2007; Keith, 2008; Albaneze-Walker et al., 2009; Shirbin et al., 2010; Cívicos et al., 2011; Cívicos et al., 2012; Kovacs et al., 2012; Cívicos et al., 2013; Potter et al., 2016; Huang et al., 2021; Zhang et al., 2022) including nucleophilic substitution reactions (Kwon et al., 2020; Bolding et al., 2022). In addition, imidazole-1-sulfonyl azide is widely adopted in synthetic chemistry as an inexpensive, stable, and effective alternative to triflyl azide as a diazotransfer reagent. See Goddard-Borger & Stick, 2007; Potter et al., 2016). Attorney Docket No.: 3062 / 203 PCT The biological applications of imidazoles are exemplified by the role of this heterocycle as a side chain group of histidine residues on proteins. See Fox, 1943; Polgar, 2005; Agback & Agback, 2018; Moro et al., 2020. Notably, histidine mediates important acid-base chemistry in the active site of enzymes to enhance the nucleophilicity of catalytic serines in proteases, esterases, lipases, and other members of the serine hydrolase superfamily. See Satoh & Hosokawa, 1998; Holm et al., 2000; Polgar, 2005; Satoh & Hosokawa, 2006; Ross & Crow, 2007; Long & Cravatt, 2011; Agback & Agback, 2018; Wang et al., 2018; Wu et al., 2021). Imidazoles are also important components of neurotransmitters including histamine. See Haas et al., 2008; Thangam et al., 2018. The importance of imidazoles for molecular recognition in biological systems is further illustrated by its prevalence as a component of drugs that modulate a variety of proteins involved in inflammation, infectious disease, and cancer. See Sundberg & Martin, 1974; Verma et al., 2013; Zhang et al., 2014; Alghamdi et al., 2021. To date, the sulfonyl- and sulfonate-imidazole unit serves as a relatively inert nucleofuge but has demonstrated leaving group (LG) capabilities when activated, for example, to the imidazolium ion for amine coupling reactions. See Monjoint & Ruasse, 1984; O’Connell & Rapoport, 2002; Pearson et al., 2002, Reyes-Rangel, et al., 2016. For biological studies and chemical proteomics specifically, only a handful of applications of imidazole as a LG have been reported. See Cruite et al., 2023. See also PCT International Patent Application Publication No.2020 / 214336, the contents of which are incorporated herein by reference in its entirety. For example, Huang et al. explored protein interactions with the clinical candidate but neural toxic drug BIA 10-2474, using a similar structured acyl imidazole probe (Huang et al., 2019). The Hamachi group discovered Ligand-Directed Acyl Imidazole (LDAI) chemistry, where target selectivity has been achieved via high ligand specificity and controllable reactivity of the alkyloxyacyl imidazole linker. See Fujishima et al., 2012; Matsuo et al., 2013; Yamaura et al., 2016. The Hamachi group recently reported the utility of LDAI for drug and target discovery. For example, ligand-directed labeling of α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA)-activated subtype of the glutamate receptor family (AMPAR) was achieved in neurons both in situ and in vivo. See Wakayama et al., 2017. Tamura et al. reported ligand-directed labeling using an N-acyl-N-alkyl sulfonamide in live cells, exemplified by selective labeling of K58 in Hsp90α. See Tamura et al., 2018. Recent applications of acyl imidazoles utilized copper-dependent bioconjugation of proximal proteins at sites of elevated labile copper in live cells. See Lee et al., 2020. Attorney Docket No.: 3062 / 203 PCT As disclosed herein, a series of imidazole-1-sulfonyl and -sulfonate probes have been developed to investigate the chemical reactivity and application of this compound class for chemoproteomics. It was found that the imidazolium functioned as a ‘supercharged’ nucleofuge that broadly reacted with nucleophiles in solution but did not appear suitable for biological applications because of stability issues. On the opposite end of the reactivity spectrum, sulfonate imidazoles (Imates) were largely inert against nucleophiles in solution and proteomes. Aryl sulfonyl imidazoles (Imyl), however, exhibited a tempered reactivity that could be tuned, for example, by substitutions at the 4-position of the imidazole nucleofuge, for covalent binding to lysine and tyrosine sites on proteins in live cells. Accordingly, in some embodiments, the presently disclosed subject matter provides a compound having a structure of Formula (I) or Formula (I’): wherein: G2 is selected from the group comprising H, halo, alkyl, substituted alkyl, perhaloalkyl, aralkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; G3is alkyl, optionally methyl; G4 is selected from the group comprising alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocycyl, aralkyl, substituted aralkyl, substituted aryloxy, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; and Aˉ is present or absent, wherein when G3is alkyl, Aˉ is present and is an anionic group, optionally trifluoromethanesulfonate anion (OTf), and where G3 is Oˉ, Aˉ is absent. In some embodiments, the compound is selected from the group comprising KY-2, KY-5, KY-342, KY-6, Imyl-01+, Imate-01; RJG-3017, and RJG-3016. In some embodiments, the presently disclosed subject matter provides a compound selected from the group comprising RJG-2096, Tet-02, Tet-03, and Tet-04. In some embodiments, the presently disclosed compounds are provided in the form of pharmaceutically acceptable salts or solvates. Attorney Docket No.: 3062 / 203 PCT II.B. Pharmaceutical Compositions and Administration The presently disclosed subject matter also relates, in some embodiments, to pharmaceutical compositions comprising, consisting essentially of, or consisting of one or more compounds of the presently disclosed subject matter and a pharmaceutically acceptable carrier, diluent, and / or excipient. Pharmaceutical compositions comprising the present compounds are administered to a subject in need thereof by any number of routes including, but not limited to, topical, oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual, or rectal means. As such, in some embodiments the presently disclosed compositions are administered by injecting the composition subcutaneously, intraperitoneally, into adipose tissue, and / or intramuscularly into the subject. In accordance with some embodiments, a method for treating a subject in need of such treatment is provided. The method comprises administering a pharmaceutical composition comprising at least one compound of the presently disclosed subject matter to a subject in need thereof. Compounds identified by the methods of the presently disclosed subject matter can be administered with known compounds or other medications as well. The pharmaceutical compositions useful for practicing the presently disclosed subject matter may be administered to deliver a dose of between 1 ng / kg / day and 100 mg / kg / day. The presently disclosed subject matter encompasses the preparation and use of pharmaceutical compositions comprising a compound useful for treatment of the diseases and disorders disclosed herein as an active ingredient. Such a pharmaceutical composition may consist of the active ingredient alone, in a form suitable for administration to a subject, or the pharmaceutical composition may comprise the active ingredient and one or more pharmaceutically acceptable carriers, one or more additional ingredients, or some combination of these. The active ingredient may be present in the pharmaceutical composition in the form of a physiologically acceptable ester or salt, such as in combination with a physiologically acceptable cation or anion, as is well known in the art. As used herein, the term “physiologically acceptable” ester or salt means an ester or salt form of the active ingredient which is compatible with any other ingredients of the pharmaceutical composition, which is not deleterious to the subject to which the composition is to be administered. Attorney Docket No.: 3062 / 203 PCT The compositions of the presently disclosed subject matter may comprise at least one active peptide, one or more acceptable carriers, and optionally other peptides or therapeutic agents. For in vivo applications, the compositions of the presently disclosed subject matter may comprise a pharmaceutically acceptable salt. Suitable acids which are capable of forming such salts with the compounds of the presently disclosed subject matter include inorganic acids such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfuric acid, phosphoric acid and the like; and organic acids such as formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, anthranilic acid, cinnamic acid, naphthalene sulfonic acid, sulfanilic acid and the like. Pharmaceutically acceptable carriers include physiologically tolerable or acceptable diluents, excipients, solvents, or adjuvants. The compositions are in some embodiments sterile and nonpyrogenic. Examples of suitable carriers include, but are not limited to, water, normal saline, dextrose, mannitol, lactose or other sugars, lecithin, albumin, sodium glutamate, cysteine hydrochloride, ethanol, polyols (propylene glycol, polyethylene glycol, glycerol, and the like), vegetable oils (such as olive oil), injectable organic esters such as ethyl oleate, ethoxylated isosteraryl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methahydroxide, bentonite, kaolin, agar-agar and tragacanth, or mixtures of these substances, and the like. In some embodiments wherein a composition of the presently disclosed subject matter is desired to induce an immune response, the compositions of the presently disclosed subject matter can further comprise an adjuvant. In some embodiments, the at least one adjuvant is selected from the group consisting of montanide ISA-51 (Seppic, Inc.), QS-21 (Aquila Pharmaceuticals, Inc.), tetanus helper peptides, GM-CSF, cyclophosamide, bacillus Calmette- Guerin (BCG), corynbacterium parvum, levamisole, azimezone, isoprinisone, dinitrochlorobenezene (DNCB), keyhole limpet hemocyanins (KLH), Freunds adjuvant (complete and incomplete), mineral gels, aluminum hydroxide (Alum), lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, diphtheria toxin (DT). The pharmaceutical compositions may also contain minor amounts of nontoxic auxiliary pharmaceutical substances or excipients and / or additives, such as wetting agents, emulsifying agents, pH buffering agents, antibacterial and antifungal agents (such as parabens, chlorobutanol, phenol, sorbic acid, and the like). Suitable additives include, but are not limited to, physiologically biocompatible buffers (e.g., tromethamine hydrochloride), additions (e.g., Attorney Docket No.: 3062 / 203 PCT 0.01 to 10 mole percent) of chelants (such as, for example, DTPA or DTPA-bisamide) or calcium chelate complexes (as for example calcium DTPA or CaNaDTPA-bisamide), or, optionally, additions (e.g., 1 to 50 mole percent) of calcium or sodium salts (for example, calcium chloride, calcium ascorbate, calcium gluconate or calcium lactate). If desired, absorption enhancing or delaying agents (such as liposomes, aluminum monostearate, or gelatin) may be used. The compositions can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution or suspension in liquid prior to injection, or as emulsions. Pharmaceutical compositions according to the presently disclosed subject matter can be prepared in a manner fully within the skill of the art. The compositions of the presently disclosed subject matter, pharmaceutically acceptable salts thereof, or pharmaceutical compositions comprising these compounds can be so that the compounds can have a physiological effect. Administration can occur enterally or parenterally; for example, orally, rectally, intracisternally, intravaginally, intraperitoneally, locally (e.g., with powders, ointments, or drops), or as a buccal or nasal spray or aerosol. Parenteral administration is preferred. Particularly preferred parenteral administration methods include intravascular administration (e.g., intravenous bolus injection, intravenous infusion, intra-arterial bolus injection, intra-arterial infusion, and catheter instillation into the vasculature), peri- and intra-target tissue injection, subcutaneous injection or deposition including subcutaneous infusion, intramuscular injection, and direct application to the target area, for example by a catheter or other placement device. Where the administration is by injection or direct application, the injection or direct application can be in a single dose or in multiple doses. Where the administration of the compound is by infusion, the infusion can be a single sustained dose over a prolonged period of time or multiple infusions. The formulations of the pharmaceutical compositions described herein may be prepared by any method known or hereafter developed in the art of pharmacology. In general, such preparatory methods include the step of bringing the active ingredient into association with a carrier or one or more other accessory ingredients, and then, if necessary or desirable, shaping or packaging the product into a desired single- or multi-dose unit. It will be understood by the skilled artisan that such pharmaceutical compositions are generally suitable for administration to animals of all sorts. Subjects to which administration of the pharmaceutical compositions of the presently disclosed subject matter is contemplated include, but are not limited to, humans and other primates, mammals including commercially Attorney Docket No.: 3062 / 203 PCT relevant mammals such as cattle, pigs, horses, sheep, cats, and dogs, birds including commercially relevant birds such as chickens, ducks, geese, and turkeys. A pharmaceutical composition of the presently disclosed subject matter may be prepared, packaged, or sold in bulk, as a single unit dose, or as a plurality of single unit doses. As used herein, a “unit dose” is a discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject or a convenient fraction of such a dosage such as, for example, one-half or one- third of such a dosage. The relative amounts of the active ingredient, the pharmaceutically acceptable carrier, and any additional ingredients in a pharmaceutical composition of the presently disclosed subject matter will vary, depending upon the identity, size, and condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1% and 100% (w / w) active ingredient. In addition to the active ingredient, a pharmaceutical composition of the presently disclosed subject matter may further comprise one or more additional pharmaceutically active agents. Particularly contemplated additional agents include anti-emetics and scavengers such as cyanide and cyanate scavengers. Controlled- or sustained-release formulations of a pharmaceutical composition of the presently disclosed subject matter may be made using conventional technology. As used herein, “additional ingredients” include, but are not limited to, one or more of the following: excipients; surface active agents; dispersing agents; inert diluents; granulating and disintegrating agents; binding agents; lubricating agents; sweetening agents; flavoring agents; coloring agents; preservatives; physiologically degradable compositions such as gelatin; aqueous vehicles and solvents; oily vehicles and solvents; suspending agents; dispersing or wetting agents; emulsifying agents, demulcents; buffers; salts; thickening agents; fillers; emulsifying agents; antioxidants; antibiotics; antifungal agents; stabilizing agents; and pharmaceutically acceptable polymeric or hydrophobic materials. Other “additional ingredients” which may be included in the pharmaceutical compositions of the presently disclosed subject matter are known in the art and described, for example in Gennaro, 1985; Gennaro, 1990; or Gennaro, 2003; each of which is incorporated herein by reference. Typically, dosages of the compound of the presently disclosed subject matter which may be administered to an animal, in some embodiments a human, range in amount from 1 μg Attorney Docket No.: 3062 / 203 PCT to about 100 g per kilogram of body weight of the animal. While the precise dosage administered will vary depending upon any number of factors, including but not limited to, the type of animal and type of disease state being treated, the age of the animal and the route of administration. In some embodiments, the dosage of the compound will vary from about 1 mg to about 10 g per kilogram of body weight of the animal. In another aspect, the dosage will vary from about 10 mg to about 1 g per kilogram of body weight of the animal. The compound may be administered to an animal as frequently as several times daily, or it may be administered less frequently, such as once a day, once a week, once every two weeks, once a month, or even less frequently, such as once every several months or even once a year or less. The frequency of the dose will be readily apparent to the skilled artisan and will depend upon any number of factors, such as, but not limited to, the type of cancer being diagnosed, the type and severity of the condition or disease being treated, the type and age of the animal, etc. Suitable preparations include injectables, either as liquid solutions or suspensions, however, solid forms suitable for solution in, suspension in, liquid prior to injection, may also be prepared. The preparation may also be emulsified, or the polypeptides encapsulated in liposomes. The active ingredients are often mixed with excipients which are pharmaceutically acceptable and compatible with the active ingredient. Suitable excipients are, for example, water saline, dextrose, glycerol, ethanol, or the like and combinations thereof. In addition, if desired, the vaccine preparation may also include minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, and / or adjuvants. The presently disclosed subject matter also includes a kit comprising the composition of the presently disclosed subject matter and an instructional material which describes administering the composition to a subject. In some embodiments, this kit comprises a (in some embodiments sterile) solvent suitable for dissolving or suspending the composition of the presently disclosed subject matter prior to administering the compound to the subject. As used herein, an “instructional material” includes a publication, a recording, a diagram, or any other medium of expression which can be used to communicate the usefulness of a composition of the presently disclosed subject matter in the kit for effecting alleviation of the various diseases or disorders recited herein. Optionally, or alternately, the instructional material may describe one or more methods of using the compositions for diagnostic or identification purposes or of alleviation the diseases or disorders in a cell or a tissue of a mammal. The instructional material of the kit of the presently disclosed subject matter may, Attorney Docket No.: 3062 / 203 PCT for example, be affixed to a container which contains a composition of the presently disclosed subject matter or be shipped together with a container which contains the composition. Alternatively, the instructional material may be shipped separately from the container with the intention that the instructional material and the compound be used cooperatively by the recipient. The presently disclosed subject matter also related to methods for using the compositions of the presently disclosed subject matter for various purposes. For example, in some embodiments the presently disclosed subject matter also relates to methods for treating and / or preventing diseases, disorders, and / or conditions associated with inflammation. II.C. Dosages An effective dose of a composition of the presently disclosed subject matter is administered to a subject in need thereof. A “treatment effective amount” or a “therapeutic amount” is an amount of a therapeutic composition sufficient to produce a measurable response (e.g., a biologically or clinically relevant response in a subject being treated, such as but not limited to a reduction in scarring and / or fibrosis, particularly as compared to the same subject had the subject not received the composition). Actual dosage levels of active ingredients in the compositions of the presently disclosed subject matter can be varied so as to administer an amount of the active compound(s) that is effective to achieve the desired therapeutic response for a particular subject. The selected dosage level will depend upon the activity of the composition, the route of administration, combination with other drugs or treatments, the severity of the disease, disorder, and / or condition being treated, and the condition and prior medical history of the subject being treated. However, it is within the skill of the art to start doses of the compositions of the presently disclosed subject matter at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. The potency of a composition can vary, and therefore a “treatment effective amount” can vary. However, using the methods described herein, one skilled in the art can readily assess the potency and efficacy of a composition of the presently disclosed subject matter and adjust the therapeutic regimen accordingly. After review of the disclosure of the presently disclosed subject matter presented herein, one of ordinary skill in the art can tailor the dosages to an individual subject, taking into account the particular formulation, method of administration to be used with the composition, and particular disease, disorder, and / or condition treated. Further calculations of dose can consider subject height and weight, severity and stage of symptoms, and the presence of additional Attorney Docket No.: 3062 / 203 PCT deleterious physical conditions. Such adjustments or variations, as well as evaluation of when and how to make such adjustments or variations, are well known to those of ordinary skill in the art of medicine. II.D. Routes of Administration Suitable methods for administration of the compositions of the presently disclosed subject matter include, but are not limited to intravenous administration, oral delivery, and delivery directly to a target tissue or organ (e.g., a topical application and / or a site of injury such as but not limited to a muscle injury). Exemplary routes of administration include parenteral, enteral, intravenous, intraarterial, intracardiac, intrapericardial, intraosseal, intracutaneous, subcutaneous, intradermal, subdermal, transdermal, intrathecal, intramuscular, intraperitoneal, intrasternal, parenchymatous, oral, sublingual, buccal, inhalational, and intranasal. The selection of a particular route of administration can be made based at least in part on the nature of the formulation and the ultimate target site where the compositions of the presently disclosed subject matter are desired to act. In some embodiments, the method of administration encompasses features for regionalized delivery or accumulation of the compositions at the site in need of treatment. In some embodiments, the compositions are delivered directly into the site to be treated. By way of example and not limitation, in some embodiments a composition of the presently disclosed subject matter is administered to the subject via a route selected from the group consisting of intraperitoneal, intramuscular, intravenous, and intranasal, or any combination thereof. The methods described herein use pharmaceutical compositions comprising the molecules described above, together with one or more pharmaceutically acceptable excipients or vehicles, and optionally other therapeutic and / or prophylactic ingredients. Such excipients include liquids such as water, saline, glycerol, polyethylene glycol, hyaluronic acid, ethanol, cyclodextrins, modified cyclodextrins (i.e., sufobutyl ether cyclodextrins), etc. Suitable excipients for non-liquid formulations are also known to those of skill in the art. Pharmaceutically acceptable salts can be used in the compositions of the present invention and include, for example, mineral acid salts such as hydrochlorides, hydrobromides, phosphates, sulfates, and the like; and the salts of organic acids such as acetates, propionates, malonates, benzoates, and the like. Additionally, auxiliary substances, such as wetting or emulsifying agents, biological buffering substances, surfactants, and the like, may be present in such vehicles. A biological buffer can be virtually any solution which is pharmacologically acceptable and which provides Attorney Docket No.: 3062 / 203 PCT the formulation with the desired pH, i.e., a pH in the physiologically acceptable range. Examples of buffer solutions include saline, phosphate buffered saline, Tris buffered saline, Hank’s buffered saline, and the like. Depending on the intended mode of administration, the pharmaceutical compositions may be in the form of a liquid, suspension, cream, ointment, lotion, or the like, preferably in unit dosage form suitable for single administration of a precise dosage. The compositions can in some embodiments include one or more pharmaceutically acceptable carriers and, in addition, may include other pharmaceutical agents, adjuvants, diluents, buffers, etc. III. Methods of Covalently Modifying Proteins Small molecules can serve as versatile tools for perturbing the functions of peptides and proteins in biological systems. Many human proteins currently lack selective chemical ligands; and there are several classes of proteins that are currently considered as undruggable. In some embodiments, the presently disclosed compounds can be used as covalent ligands to expand the landscape of proteins amenable to targeting by small molecules. In some instances, the compounds provide covalent ligands that combine features of recognition and reactivity, thereby providing for the selective targeting of sites on proteins of interest, including those that are difficult to address by reversible binding interactions alone and / or with other types of covalent ligands. In some embodiments, the compound is selected from KY-2, KY-5, KY-342, KY-6, RJG-2096, RJG-3017, and RJG-3016. In some embodiments, the presently disclosed subject matter provides a method of covalently modifying a protein or peptide in a sample, wherein the method comprises contacting the sample with a compound disclosed herein (e.g., a compound of Formula (I) or (I’)), thereby providing a covalently modified peptide or protein. In some embodiments, the contacting provides a covalent modified peptide or protein, wherein said covalently modified peptide or protein comprises one or more covalently modified tyrosine or covalently modified lysine residues, wherein the covalently modified tyrosine or covalently modified lysine residues comprise a structure: Attorney Docket No.: 3062 / 203 PCT wherein G4 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocycyl, aralkyl, substituted aralkyl, aryl, substituted aryloxy, aryl, substituted aryl, heteroaryl, and substituted heteroaryl. In some embodiments, G4is substituted phenyl. In some embodiments, the sample is a biological sample. In some embodiments, covalently modifying the protein or peptide modulates a biological activity of the protein or peptide. In some embodiments, modifying the protein or peptide inhibits or activates a biological activity of the protein or peptide. For example, in some embodiments, the protein is an enzyme and covalently modifying the enzyme with the compound inhibits the enzyme. In some embodiments, modulating the activity of a protein comprises enhancing or reducing the ability of the protein to interact with other compounds, such as other proteins. Thus, in some embodiments, the modulation results in reducing the protein-protein interactions of the protein comprising the reactive amino acid. In some embodiments, modulating the activity of a protein comprising a comprises inhibiting, blocking (partially or substantially completely) or disrupting a protein-RNA interaction, a protein-DNA interaction, a protein-lipid interaction, and / or a protein-metabolite interaction of the protein. Thus, in accordance with some embodiments of the presently disclosed subject matter, the presently disclosed ligands can serve as tools for the global investigation of protein function. In some embodiments, the protein or peptide is selected from the group comprising, but not limited to, a GST (e.g., GSTP1), PTGR2, AKR1C1, and ALDH3A1. In some embodiments, the sample comprises an isolated protein. In some embodiments, the sample comprises a cell lysate, a biological fluid (e.g., saliva, ascites, blood, urine, etc.) or a live cell. In some embodiments, the sample comprising living cells comprises an organ, or a living organism (e.g., a subject, such as a human or other mammal). IV. Methods of Identifying Reactive Amino Acid Residues In some embodiments, the presently disclosed subject matter provides a method of identifying a reactive amino acid residue of a protein, the method comprising: providing a protein sample comprising isolated proteins, living cells, or a cell lysate; (b) contacting the protein sample with a probe compound as disclosed herein for a period of time sufficient for the compound to react with at least one reactive amino acid residue (e.g., a tyrosine or lysine Attorney Docket No.: 3062 / 203 PCT residue) in a protein in the protein sample, thereby forming at least one modified reactive amino acid residue; and (c) analyzing proteins in the protein sample to identify at least one modified reactive amino acid residue, thereby identifying at least one reactive amino acid residue of a protein. In some embodiments, the analyzing of step (c) further comprises tagging the at least one modified reactive amino acid residue with a compound comprising a detectable labeling group, thereby forming at least one tagged reactive amino acid residue comprising said detectable labeling group. In some embodiments, the detectable labeling group comprises biotin or a biotin derivative. In some embodiments, the biotin derivative is desthiobiotin. In some embodiments, the tagging comprises reacting an alkyne group of at least one tagged reactive amino acid residue with a compound comprising both an azide moiety (or other alkyne-reactive group) and a detectable labeling group (e.g., biotin or a biotin derivative). In some embodiments, the compound comprising the azide moiety and the detectable labeling group further comprises an alkylene linker, which in some embodiments, can comprise a polyether group, such as an oligomer of methylene glycol, ethylene glycol or propylene glycol (e.g., a group having the formula –(O-C2H4-)x-). In some embodiments, the tagging comprises performing a copper-catalyzed azide-alkyne cycloaddition (CuAAC) coupling reaction. In some embodiments, the analyzing further comprises digesting the protein sample to provide a digested protein sample comprising a protein fragment comprising the at least one tagged reactive amino acid residue comprising the detectable group. In some embodiments, the digesting is performed with a peptidase. In some embodiments, the digesting is performed with trypsin. In some embodiments, the analyzing further comprises enriching the digested protein sample for the detectable labeling group. For example, in some embodiments, the enriching comprises contacting the digested protein sample with a solid support comprising a binding partner of the detectable labeling group. In some embodiments, when the detectable labeling group comprises biotin or a derivative thereof, the solid support comprises streptavidin. In some embodiments, the analyzing further comprises analyzing the digested protein sample (e.g., the enriched digested protein sample) via liquid chromatography-mass spectrometry or via a gel-based assay. In some embodiments, providing the protein sample further comprises separating the protein sample into a first protein sample and a second protein sample. Then, in the contacting step, the first protein sample can be contacted with a first probe compound at a first probe concentration for a first period of time and the second protein sample can be contacted with a Attorney Docket No.: 3062 / 203 PCT second probe compound (e.g., a second probe compound having a different structure than that of the first probe compound) at the same probe concentration (i.e., at the first probe concentration) for the same time period (i.e., for the first period of time). Alternatively, the second protein sample can be contacted with the same probe compound as the first protein sample, but at a different probe concentration (i.e., a second probe concentration) or for a different period of time. In some embodiments, analyzing proteins comprises analyzing the first and second protein samples to determine the presence and / or identity of a modified reactive amino acid residue in the first sample and the presence and / or identity of a modified reactive amino acid residue in the second sample. In some embodiments, the identities and / or amounts of identified modified reactive amino acid residues from the first and second protein samples are compared. In some embodiments, the protein sample comprises living cells. In some embodiments, providing the protein sample further comprises separating the protein sample into a first protein sample and a second protein sample and culturing the first protein sample in a first cell culture medium comprising heavy isotopes prior to the contacting of step (b) and culturing the second protein sample in a second cell culture medium, wherein the second culture medium comprises a naturally occurring isotope distribution prior to the contacting of step (b). In some embodiments, the first cell culture medium comprises13C- and / or15N-labeled amino acids. In some embodiments, the first cell culture medium comprises13C-,15N-labeled lysine and arginine. In some embodiments, e.g., if the protein sample does not comprise living cells, the probe compound can comprise a detectable labeling group comprising a heavy isotope (e.g., a13C label) or the method can comprise tagging the at least one modified amino acid residue with a detectable labeling group comprising a heavy isotope. In some embodiments, the protein sample is separated into a first and a second protein sample and one of the first and the second protein sample is cultured in the presences of an inhibitor of a protein of interest. V. Cells, Analytical Techniques, and Instrumentation In some embodiments, one or more of the methods disclosed herein comprise a sample (e.g., a cell sample, cell lysate sample or a biological organism). In some embodiments, the sample for use with the methods described herein is obtained from cells of an animal. In some instances, the animal cell includes a cell from a marine invertebrate, fish, insects, amphibian, reptile, or mammal. In some instances, the mammalian cell is a primate, ape, equine, bovine, Attorney Docket No.: 3062 / 203 PCT porcine, canine, feline, or rodent. In some instances, the mammal is a primate, ape, dog, cat, rabbit, ferret, or the like. In some cases, the rodent is a mouse, rat, hamster, gerbil, hamster, chinchilla, or guinea pig. In some embodiments, the bird cell is from a canary, parakeet or parrots. In some embodiments, the reptile cell is from a turtles, lizard or snake. In some cases, the fish cell is from a tropical fish. In some cases, the fish cell is from a zebrafish (e.g., Danino rerio). In some cases, the worm cell is from a nematode (e.g., C. elegans). In some cases, the amphibian cell is from a frog. In some embodiments, the arthropod cell is from a tarantula or hermit crab. In some embodiments, the sample for use with the methods described herein is obtained from a mammalian cell. In some instances, the mammalian cell is an epithelial cell, connective tissue cell, hormone secreting cell, a nerve cell, a skeletal muscle cell, a blood cell, or an immune system cell. Exemplary mammalian cell lines include, but are not limited to, 293A cells, 293FT cells, 293F cells, 293H cells, HEK 293 cells, CHO DG44 cells, CHO-S cells, CHO-K1 cells, and PC12 cells. In some embodiments, the sample for use with the methods described herein is obtained from cells of a tumor cell line. In some instances, the sample is obtained from cells of a solid tumor cell line. In some instances, the solid tumor cell line is a sarcoma cell line. In some instances, the solid tumor cell line is a carcinoma cell line. In some embodiments, the sarcoma cell line is obtained from a cell line of alveolar rhabdomyosarcoma, alveolar soft part sarcoma, ameloblastoma, angiosarcoma, chondrosarcoma, chordoma, clear cell sarcoma of soft tissue, dedifferentiated liposarcoma, desmoid, desmoplastic small round cell tumor, embryonal rhabdomyosarcoma, epithelioid fibrosarcoma, epithelioid hemangioendothelioma, epithelioid sarcoma, esthesioneuroblastoma, Ewing sarcoma, extrarenal rhabdoid tumor, extraskeletal myxoid chondrosarcoma, extraskeletal osteosarcoma, fibrosarcoma, giant cell tumor, hemangiopericytoma, infantile fibrosarcoma, inflammatory myofibroblastic tumor, Kaposi sarcoma, leiomyosarcoma of bone, liposarcoma, liposarcoma of bone, malignant fibrous histiocytoma (MFH), malignant fibrous histiocytoma (MFH) of bone, malignant mesenchymoma, malignant peripheral nerve sheath tumor, mesenchymal chondrosarcoma, myxofibrosarcoma, myxoid liposarcoma, myxoinflammatory fibroblastic sarcoma, neoplasms with perivascular epitheioid cell differentiation, osteosarcoma, parosteal osteosarcoma, neoplasm with perivascular epitheioid cell differentiation, periosteal osteosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, PNET / extraskeletal Ewing tumor, Attorney Docket No.: 3062 / 203 PCT rhabdomyosarcoma, round cell liposarcoma, small cell osteosarcoma, solitary fibrous tumor, synovial sarcoma, and telangiectatic osteosarcoma. In some embodiments, the carcinoma cell line is obtained from a cell line of adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, anaplastic carcinoma, large cell carcinoma, small cell carcinoma, anal cancer, appendix cancer, bile duct cancer (i.e., cholangiocarcinoma), bladder cancer, brain tumor, breast cancer, cervical cancer, colon cancer, cancer of Unknown Primary (CUP), esophageal cancer, eye cancer, fallopian tube cancer, gastroenterological cancer, kidney cancer, liver cancer, lung cancer, medulloblastoma, melanoma, oral cancer, ovarian cancer, pancreatic cancer, parathyroid disease, penile cancer, pituitary tumor, prostate cancer, rectal cancer, skin cancer, stomach cancer, testicular cancer, throat cancer, thyroid cancer, uterine cancer, vaginal cancer, or vulvar cancer. In some instances, the sample is obtained from cells of a hematologic malignant cell line. In some instances, the hematologic malignant cell line is a T-cell cell line. In some instances, B-cell cell line. In some instances, the hematologic malignant cell line is obtained from a T-cell cell line of: peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma, angioimmunoblastic lymphoma, cutaneous T-cell lymphoma, adult T-cell leukemia / lymphoma (ATLL), blastic NK-cell lymphoma, enteropathy-type T-cell lymphoma, hematosplenic gamma-delta T-cell lymphoma, lymphoblastic lymphoma, nasal NK / T-cell lymphomas, or treatment-related T-cell lymphomas. In some instances, the hematologic malignant cell line is obtained from a B-cell cell line of: acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute monocytic leukemia (AMoL), chronic lymphocytic leukemia (CLL), high-risk chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), high-risk small lymphocytic lymphoma (SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), Waldenstrom’s macroglobulinemia, multiple myeloma, extranodal marginal zone B cell lymphoma, nodal marginal zone B cell lymphoma, Burkitt’s lymphoma, non-Burkitt high grade B cell lymphoma, primary mediastinal B-cell lymphoma (PMBL), immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, B cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, mediastinal (thymic) large B cell lymphoma, intravascular large B cell lymphoma, primary effusion lymphoma, or lymphomatoid granulomatosis. Attorney Docket No.: 3062 / 203 PCT In some embodiments, the sample for use with the methods described herein is obtained from a tumor cell line. Exemplary tumor cell lines include, but are not limited to, 600MPE, AU565, BT-20, BT-474, BT-483, BT-549, Evsa-T, Hs578T, MCF-7, MDA-MB-231, SkBr3, T-47D, HeLa, DU145, PC3, LNCaP, A549, H1299, NCI-H460, A2780, SKOV-3 / Luc, Neuro2a, RKO, RKO-AS45-1, HT-29, SW1417, SW948, DLD-1, SW480, Capan-1, MC / 9, B72.3, B25.2, B6.2, B38.1, DMS 153, SU.86.86, SNU-182, SNU-423, SNU-449, SNU-475, SNU-387, Hs 817.T, LMH, LMH / 2A, SNU-398, PLHC-1, HepG2 / SF, OCI-Ly1, OCI-Ly2, OCI-Ly3, OCI-Ly4, OCI-Ly6, OCI-Ly7, OCI-Ly10, OCI-Ly18, OCI-Ly19, U2932, DB, HBL- 1, RIVA, SUDHL2, TMD8, MEC1, MEC2, 8E5, CCRF-CEM, MOLT-3, TALL-104, AML- 193, THP-1, BDCM, HL-60, Jurkat, RPMI 8226, MOLT-4, RS4, K-562, KASUMI-1, Daudi, GA-10, Raji, JeKo-1, NK-92, and Mino. In some embodiments, the sample for use in the methods is from any tissue or fluid from an individual. Samples include, but are not limited to, tissue (e.g., connective tissue, muscle tissue, nervous tissue, or epithelial tissue), whole blood, dissociated bone marrow, bone marrow aspirate, pleural fluid, peritoneal fluid, central spinal fluid, abdominal fluid, pancreatic fluid, cerebrospinal fluid, brain fluid, ascites, pericardial fluid, urine, saliva, bronchial lavage, sweat, tears, ear flow, sputum, hydrocele fluid, semen, vaginal flow, milk, amniotic fluid, and secretions of respiratory, intestinal or genitourinary tract. In some embodiments, the sample is a tissue sample, such as a sample obtained from a biopsy or a tumor tissue sample. In some embodiments, the sample is a blood serum sample. In some embodiments, the sample is a blood cell sample containing one or more peripheral blood mononuclear cells (PBMCs). In some embodiments, the sample contains one or more circulating tumor cells (CTCs). In some embodiments, the sample contains one or more disseminated tumor cells (DTC, e.g., in a bone marrow aspirate sample). In some embodiments, the samples are obtained from the individual by any suitable means of obtaining the sample using well-known and routine clinical methods. Procedures for obtaining tissue samples from an individual are well known. For example, procedures for drawing and processing tissue sample such as from a needle aspiration biopsy is well-known and is employed to obtain a sample for use in the methods provided. Typically, for collection of such a tissue sample, a thin hollow needle is inserted into a mass such as a tumor mass for sampling of cells that, after being stained, will be examined under a microscope. In some embodiments, the sample is a biological organism. In some embodiments, the biological organism is a rodent, e.g., a mouse or a rat. In some embodiments, the biological Attorney Docket No.: 3062 / 203 PCT organism is a primate, e.g., a monkey. In some embodiments, the biological organism is a bacteria or a fungi. VI. Sample Preparation and Analysis In some embodiments, the sample (e.g., cell sample, cell lysate sample, or comprising isolated proteins) is a sample solution. In some instances, the sample solution comprises a solution such as a buffer (e.g., phosphate buffered saline) or a media. In some embodiments, the media is an isotopically labeled media. In some instances, the sample solution is a cell solution. In some embodiments, the sample (e.g., cell sample, cell lysate sample, or comprising isolated proteins) is incubated with one or more compound probes for analysis of protein-probe interactions. In some instances, the sample (e.g., cell sample, cell lysate sample, or comprising isolated proteins) is further incubated in the presence of an additional compound probe prior to addition of the one or more probes. In other instances, the sample (e.g., cell sample, cell lysate sample, or comprising isolated proteins) is further incubated with a non-probe small molecule ligand, in which the non-probe small molecule ligand does not contain a photoreactive moiety and / or an alkyne group. In such instances, the sample is incubated with a probe and non-probe small molecule ligand for competitive protein profiling analysis. In some cases, the sample is compared with a control. In some cases, a difference is observed between a set of probe protein interactions between the sample and the control. In some instances, the difference correlates to the interaction between the small molecule fragment and the proteins. In some embodiments, one or more methods are utilized for labeling a sample (e.g., cell sample, cell lysate sample, or comprising isolated proteins) for analysis of probe protein interactions. In some instances, a method comprises labeling the sample (e.g., cell sample, cell lysate sample, or comprising isolated proteins) with an enriched media. In some cases, the sample (e.g., cell sample, cell lysate sample, or comprising isolated proteins) is labeled with isotope-labeled amino acids, such as13C or15N-labeled amino acids. In some cases, the labeled sample is further compared with a non-labeled sample to detect differences in probe protein interactions between the two samples. In some instances, this difference is a difference of a target protein and its interaction with a small molecule ligand in the labeled sample versus the non-labeled sample. In some instances, the difference is an increase, decrease or a lack of protein-probe interaction in the two samples. In some instances, the isotope-labeled method is termed SILAC, stable isotope labeling using amino acids in cell culture. Attorney Docket No.: 3062 / 203 PCT In some embodiments, a method comprises incubating a sample (e.g., cell sample, cell lysate sample, or comprising isolated proteins) with a labeling group (e.g., an isotopically labeled labeling group) to tag one or more proteins of interest for further analysis. In such cases, the detectable labeling group comprises a biotin, a streptavidin, bead, resin, a solid support, or a combination thereof, and further comprises a linker that is optionally isotopically labeled. As described above, the linker can be about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more residues in length and might further comprise a cleavage site, such as a protease cleavage site (e.g., TEV cleavage site). In some cases, the labeling group is a biotin-linker moiety, which is optionally isotopically labeled with13C and15N atoms at one or more amino acid residue positions within the linker. In some cases, the biotin-linker moiety is a isotopically-labeled TEV-tag as previously described in Huang et al., 2019. In some embodiments, an isotopic reductive dimethylation (ReDi) method is utilized for processing a sample. In some cases, the ReDi labeling method involves reacting peptides with formaldehyde to form a Schiff base, which is then reduced by cyanoborohydride. This reaction dimethylates free amino groups on N-termini and lysine side chains and monomethylates N-terminal prolines. In some cases, the ReDi labeling method comprises methylating peptides from a first processed sample with a “light” label using reagents with hydrogen atoms in their natural isotopic distribution and peptides from a second processed sample with a “heavy” label using deuterated formaldehyde and cyanoborohydride. Subsequent proteomic analysis (e.g., mass spectrometry analysis) based on a relative peptide abundance between the heavy and light peptide version might be used for analysis of probe- protein interactions. In some embodiments, isobaric tags for relative and absolute quantitation (iTRAQ) method is utilized for processing a sample. In some cases, the iTRAQ method is based on the covalent labeling of the N-terminus and side chain amines of peptides from a processed sample. In some cases, reagent such as 4-plex or 8-plex is used for labeling the peptides. In some embodiments, the probe-protein complex is further conjugated to a chromophore, such as a fluorophore. In some instances, the probe-protein complex is separated and visualized utilizing an electrophoresis system, such as through a gel electrophoresis, or a capillary electrophoresis. Exemplary gel electrophoresis includes agarose based gels, polyacrylamide based gels, or starch based gels. In some instances, the probe-protein is subjected to a native electrophoresis condition. In some instances, the probe-protein is subjected to a denaturing electrophoresis condition. Attorney Docket No.: 3062 / 203 PCT In some instances, the probe-protein after harvesting is further fragmentized to generate protein fragments. In some instances, fragmentation is generated through mechanical stress, pressure, or chemical means. In some instances, the protein from the probe-protein complexes is fragmented by a chemical means. In some embodiments, the chemical means is a protease. Exemplary proteases include, but are not limited to, serine proteases such as chymotrypsin A, penicillin G acylase precursor, dipeptidase E, DmpA aminopeptidase, subtilisin, prolyl oligopeptidase, D-Ala-D-Ala peptidase C, signal peptidase I, cytomegalovirus assemblin, Lon- A peptidase, peptidase Clp, Escherichia coli phage KIF endosialidase CIMCD self-cleaving protein, nucleoporin 145, lactoferrin, murein tetrapeptidase LD-carboxypeptidase, or rhomboid-1; threonine proteases such as ornithine acetyltransferase; cysteine proteases such as TEV protease, amidophosphoribosyltransferase precursor, gamma-glutamyl hydrolase (Rattus norvegicus), hedgehog protein, DmpA aminopeptidase, papain, bromelain, cathepsin K, calpain, caspase-1, separase, adenain, pyroglutamyl-peptidase I, sortase A, hepatitis C virus peptidase 2, sindbis virus-type nsP2 peptidase, dipeptidyl-peptidase VI, or DeSI-1 peptidase; aspartate proteases such as beta-secretase 1 (BACE1), beta-secretase 2 (BACE2), cathepsin D, cathepsin E, chymosin, napsin-A, nepenthesin, pepsin, plasmepsin, presenilin, or renin; glutamic acid proteases such as AfuGprA; and metalloproteases such as peptidase_M48. In some instances, the fragmentation is a random fragmentation. In some instances, the fragmentation generates specific lengths of protein fragments, or the shearing occurs at particular sequence of amino acid regions. In some instances, the protein fragments are further analyzed by a proteomic method such as by liquid chromatography (LC; e.g., high performance liquid chromatography), liquid chromatography-mass spectrometry (LC-MS), matrix-assisted laser desorption / ionization (MALDI-TOF), gas chromatography-mass spectrometry (GC-MS), capillary electrophoresis- mass spectrometry (CE-MS), or nuclear magnetic resonance imaging (NMR). In some embodiments, the LC method is any suitable LC methods well known in the art, for separation of a sample into its individual parts. This separation occurs based on the interaction of the sample with the mobile and stationary phases. Since there are many stationary / mobile phase combinations that are employed when separating a mixture, there are several different types of chromatography that are classified based on the physical states of those phases. In some embodiments, the LC is further classified as normal-phase chromatography, reverse-phase chromatography, size-exclusion chromatography, ion- exchange chromatography, affinity chromatography, displacement chromatography, partition Attorney Docket No.: 3062 / 203 PCT chromatography, flash chromatography, chiral chromatography, and aqueous normal-phase chromatography. In some embodiments, the LC method is a high performance liquid chromatography (HPLC) method. In some embodiments, the HPLC method is further categorized as normal- phase chromatography, reverse-phase chromatography, size-exclusion chromatography, ion- exchange chromatography, affinity chromatography, displacement chromatography, partition chromatography, chiral chromatography, and aqueous normal-phase chromatography. In some embodiments, the HPLC method of the present disclosure is performed by any standard techniques well known in the art. Exemplary HPLC methods include hydrophilic interaction liquid chromatography (HILIC), electrostatic repulsion-hydrophilic interaction liquid chromatography (ERLIC) and reverse phase liquid chromatography (RPLC). In some embodiments, the LC is coupled to a mass spectroscopy as a LC-MS method. In some embodiments, the LC-MS method includes ultra-performance liquid chromatography- electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS), ultra-performance liquid chromatography-electro spray ionization tandem mass spectrometry (UPLC-ESI-MS / MS), reverse phase liquid chromatography-mass spectrometry (RPLC-MS), hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS), hydrophilic interaction liquid chromatography-triple quadrupole tandem mass spectrometry (HILIC- QQQ), electrostatic repulsion-hydrophilic interaction liquid chromatography-mass spectrometry (ERLIC-MS), liquid chromatography time-of-flight mass spectrometry (LC- QTOF-MS), liquid chromatography-tandem mass spectrometry (LC-MS / MS), multidimensional liquid chromatography coupled with tandem mass spectrometry (LC / LC- MS / MS). In some instances, the LC-MS method is LC / LC-MS / MS. In some embodiments, the LC-MS methods of the present disclosure are performed by standard techniques well known in the art. In some embodiments, the GC is coupled to a mass spectroscopy as a GC-MS method. In some embodiments, the GC-MS method includes two-dimensional gas chromatography time-of-flight mass spectrometry (GC*GC-TOFMS), gas chromatography time-of-flight mass spectrometry (GC-QTOF-MS) and gas chromatography-tandem mass spectrometry (GC- MS / MS). In some embodiments, CE is coupled to a mass spectroscopy as a CE-MS method. In some embodiments, the CE-MS method includes capillary electrophoresis-negative electrospray ionization-mass spectrometry (CE-ESI-MS), capillary electrophoresis-negative Attorney Docket No.: 3062 / 203 PCT electrospray ionization-quadrupole time of flight-mass spectrometry (CE-ESI-QTOF-MS) and capillary electrophoresis-quadrupole time of flight-mass spectrometry (CE-QTOF-MS). In some embodiments, the nuclear magnetic resonance (NMR) method is any suitable method well known in the art for the detection of one or more cysteine binding proteins or protein fragments disclosed herein. In some embodiments, the NMR method includes one dimensional (1D) NMR methods, two dimensional (2D) NMR methods, solid state NMR methods and NMR chromatography. Exemplary 1D NMR methods include1Hydrogen,13Carbon,15Nitrogen,17Oxygen,19Fluorine,31Phosphorus,39Potassium,23Sodium,33Sulfur,87Strontium,27Aluminium,43Calcium,35Chlorine,37Chlorine,63Copper,65Copper,57Iron,25Magnesium,199Mercury or67Zinc NMR method, distortionless enhancement by polarization transfer (DEPT) method, attached proton test (APT) method and 1D-incredible natural abundance double quantum transition experiment (INADEQUATE) method. Exemplary 2D NMR methods include correlation spectroscopy (COSY), total correlation spectroscopy (TOCSY), 2D-INADEQUATE, 2D-adequate double quantum transfer experiment (ADEQUATE), nuclear overhauser effect spectroscopy (NOSEY), rotating-frame NOE spectroscopy (ROESY), heteronuclear multiple-quantum correlation spectroscopy (HMQC), heteronuclear single quantum coherence spectroscopy (HSQC), short range coupling and long range coupling methods. Exemplary solid state NMR method include solid state13Carbon NMR, high resolution magic angle spinning (HR-MAS) and cross polarization magic angle spinning (CP-MAS) NMR methods. Exemplary NMR techniques include diffusion ordered spectroscopy (DOSY), DOSY-TOCSY, and DOSY-HSQC. In some embodiments, the results from the mass spectroscopy method are analyzed by an algorithm for protein identification. In some embodiments, the algorithm combines the results from the mass spectroscopy method with a protein sequence database for protein identification. In some embodiments, the algorithm comprises ProLuCID algorithm, Probity, Scaffold, SEQUEST, or Mascot. In accordance with the presently disclosed subject matter, as described above or as discussed in the EXAMPLES below, there can be employed conventional chemical, cellular, histochemical, biochemical, molecular biology, microbiology, recombinant DNA, and clinical techniques which are known to those of skill in the art. Such techniques are explained fully in the literature. See for example, Sambrook et al., 1989; Glover, 1985; Gait, 1984; Harlow & Lane, 1988; Roe et al., 1996; and Ausubel et al., 2003. Attorney Docket No.: 3062 / 203 PCT VII. Kits / Articles of Manufacture Disclosed herein, in certain embodiments, are kits and articles of manufacture for use with one or more methods described herein. In some embodiments, described herein is a kit for generating a protein comprising a detectable group and / or a fragment of a ligand compound described herein. In some embodiments, such kit includes a probe or ligand as described herein, small molecule fragments or libraries, and / or controls, and reagents suitable for carrying out one or more of the methods described herein. In some instances, the kit further comprises samples, such as a cell sample, and suitable solutions such as buffers or media. In some embodiments, the kit further comprises recombinant proteins for use in one or more of the methods described herein. In some embodiments, additional components of the kit comprises a carrier, package, or container that is compartmentalized to receive one or more containers such as vials, tubes, and the like, each of the container(s) comprising one of the separate elements to be used in a method described herein. Suitable containers include, for example, bottles, vials, plates, syringes, and test tubes. In one embodiment, the containers are formed from a variety of materials such as glass or plastic. The articles of manufacture provided herein contain packaging materials. Examples of pharmaceutical packaging materials include, but are not limited to, bottles, tubes, bags, containers, and any packaging material suitable for a selected formulation and intended mode of use. For example, the container(s) include probes, ligands, control compounds, and one or more reagents for use in a method disclosed herein. The presently disclosed kits and articles of manufacture optionally include an identifying description or label or instructions relating to its use in the methods described herein. For example, a kit typically includes labels listing contents and / or instructions for use, and package inserts with instructions for use. A set of instructions will also typically be included. In some embodiments, a label is on or associated with the container. In some embodiments, a label is on a container when letters, numbers or other characters forming the label are attached, molded or etched into the container itself; a label is associated with a container when it is present within a receptacle or carrier that also holds the container, e.g., as a package insert. In some embodiments, a label is used to indicate that the contents are to be used for a specific therapeutic application. The label also indicates directions for use of the contents, such as in the methods described herein. Attorney Docket No.: 3062 / 203 PCT EXAMPLES The following EXAMPLES provide illustrative embodiments. In light of the present disclosure and the general level of skill in the art, those of skill will appreciate that the following EXAMPLES are intended to be exemplary only and that numerous changes, modifications, and alterations can be employed without departing from the scope of the presently disclosed subject matter. Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative EXAMPLES, make and utilize the compounds of the presently disclosed subject matter and practice the methods of the presently disclosed subject matter. The following EXAMPLES therefore particularly point out embodiments of the presently disclosed subject matter and are not to be construed as limiting in any way the remainder of the disclosure. EXAMPLE 1 Synthesis of Exemplary Sulfonyl Azole Probes and Ligands All chemicals used were reagent grade and used as supplied, except where noted. N,N- Dimethylformamide (DMF), dichloromethane (CH2Cl2), and toluene were used without any further purification steps. Analytical thin layer chromatography (TLC) was performed on Merck silica gel 60 F254 plates (0.25 mm). Flash column chromatography was carried out using forced flow of the indicated solvent on Silica Gel 60 (230-400 mesh) purchased from Fisher Scientific. Compounds were visualized by UV-irradiation and iodine chamber.1H and13C NMR spectra were recorded on a Varian Inova 500 (500 MHz), 600 (600 MHz), or Bruker Avance III 800 (800 MHz) spectrometers in CDCl3, Acetone-d6, or DMSO-d6with chemical shifts referenced to internal standards (CDCl3: 7.26 ppm1H, 77.16 ppm13C; (CD3)2CO: 2.05 ppm1H, 29.84 and 206.26 ppm13C; (CD3)2CO: 2.50 ppm1H, 40.00 ppm13C) unless stated otherwise. Splitting patterns are indicated as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad singlet for1H-NMR data. NMR chemical shifts (δ) are reported in ppm and coupling constants (J) are reported in Hz. High resolution mass spectral (HRMS) data were obtained by an Agilent 6545B LC / Q-TOF (Agilent Technologies, Santa Clara, CA, USA). High-performance liquid chromatography (HPLC) data was obtained by a Shimadzu 1100 Series spectrometer with UV detection at 254 nm using a reverse-phase column with a 10-min acidified water / acetonitrile gradient as previously described in Brulet et al., 2020. Chemical Suppliers. Propargylamine (Fisher Scientific). Water, Acetonitrile, Dichloromethane, Acetone, Ethyl acetate, n-Heptane, Hexanes, Formic acid (OPTIMA®), Attorney Docket No.: 3062 / 203 PCT Acetic acid (OPTIMA®), Sodium sulfate (Fisher Chemical). 4-bromo-1H-imidazole, 5- trifluoromethyl-1H-imidazole, methyl trifluoromethanesulfonate, 4-(chlorosulfonyl)benzoic acid, 3-phenyl-1H-pyrazole, 3-(4-methoxyphenyl)-1H-pyrazole, 3-(4-fluorophenyl)-1H- pyrazole, 4-(4-fluorophenyl)-1H-imidazole, 4-phenyl-1H-imidazole, 4-bromo-1H-imidazole (Combi-Blocks). N,N-Diisopropylethylamine (Acros Organics). 4’-methoxybiphenyl-4- sulfonyl chloride, 5-phenyl-2H-tetrazole, 5-(4-methoxyphenyl)-2H-tetrazole, 5-(4- fluorophenyl)-2H-tetrazole (Alfa Aesar). 4-methoxybenzenesulfonyl chloride, cyclopropanesulfonyl chloride, 1H-pyrazole (Oakwood Chemicals). 4’-methoxy-[1,1’- biphenyl]-4-sulfonyl chloride (1ClickChemistry).4-trifluoromethyl-1H-imidazole (Enamine). Exemplary Compounds and Procedures: 4-(Prop-2-yn-1-ylcarbamoyl)benzenesulfonyl chloride To a solution of 4-(chlorosulfonyl)benzoyl chloride (0.48 g, 2.0 mmol, 1.1 eq.) in anhydrous CH2Cl2 (8 mL, 0.25 M) was added propargyl amine (1.8 mmol, 1.0 eq.) and N,N- diisopropylethylamine (DIPEA) (249 μL, 1.8 mmol, 1.1 eq.) at -78 °C. The reaction mixture was slowly warmed to room temperature (RT). The reaction mixture was concentrated in vacuo and the crude product purified using silica gel flash column chromatography (hexane: ethyl acetate = 7: 3) to afford white solid 146.2 mg, yield = 28.3%. 4-4-hydroxy-N-(prop-2-yn-1-yl)benzamide 4-hydroxybenzoic acid (5 g, 36.2 mmol) was added to a 100 mL round bottom flask and dissolved in dichloromethane (40 mL, 0.9 M). The mixture was cooled to 0 °C in an ice bath. After cooling for 15 min, propargylamine (2.3 mL, 36.2 mmol) was added. The reaction was stirred at 0 °C for 30 min. Dicyclohexylcarbodiimide (5.7 g, 36.2 mmol) and 4- dimethylaminopyridine (440 mg, 3.62 mmol) were added to the reaction mixture. The reaction was slowly warmed to room temperature and stirred overnight. The reaction mixture was adsorbed onto Celite and the product purified by silica gel flash chromatography (10-50% gradient of ethyl acetate in hexanes) affording 2.02 g of product as a white semi-solid (33% yield). Attorney Docket No.: 3062 / 203 PCT General Protocol to synthesize sulfonyl heterocycle probes and ligands. The following procedure was used to synthesize the sulfonyl-azole probes unless specified. To a solution of sulfonyl chloride (0.2 g, 0.78 mmol, 1.1 eq.) in CH2Cl2(4 mL, 0.2 M) was added the corresponding heterocycle (0.71 mmol, 1.0 eq.) and DIPEA (136 μL, 0.78 mmol, 1.0 eq.) at room temperature. The reaction mixture was stirred at room temperature for 2 hrs. The reaction mixture was concentration in vacuo and the crude product purified using silica gel flash chromatography (10 – 40% ethyl acetate in hexanes) to afford the sulfonyl-azole product. We acknowledge the potential existence of the 1,5-substituted sulfonyl-tetrazole. We drew the 2,5- substituted sulfonyl-tetrazole given literature evidence that this is the favored regioisomer. See Efimova et al., 2009; . Sarvary & Maleki, 2015. Characterization of Representative Sulfonyl-azole Probes 4-((1H-imidazol-1-yl)sulfonyl)-N-(prop-2-yn-1-yl)benzamide (Imyl-01) White solid (72%, 324 mg)1H NMR (600 MHz, Acetone-d6) δ 8.39 (s, 1H), 8.22 (t, J = 1.1 Hz, 1H), 8.21 – 8.18 (m, 2H), 8.17 – 8.14 (m, 2H), 7.62 (t, J = 1.5 Hz, 1H), 7.11 (dd, J = 1.7, 0.8 Hz, 1H), 4.22 – 4.18 (m, 2H), 2.70 (t, J = 2.5 Hz, 1H).13C NMR (151 MHz, Acetone-d6) δ 165.4, 141.2, 138.0, 132.6, 129.9, 128.6, 118.9, 80.9, 72.4. ESI-TOF (HRMS) m / z [M+H]+calculated for C13H12N3O3S 290.0594, found 290.0602. 4-((4-phenyl-1H-imidazol-1-yl)sulfonyl)-N-(prop-2-yn-1-yl)benzamide (Imyl -02) White solid (77%, 111 mg)1H NMR (600 MHz, Acetone-d6) δ 8.34 (s, 1H), 8.28 (dd, J = 1.4, 0.6 Hz, 1H), 8.26 – 8.22 (m, 2H), 8.17 – 8.13 (m, 2H), 7.87 – 7.83 (m, 2H), 7.39 – 7.35 (m, 2H), 7.30 – 7.25 (m, 1H), 4.18 (ddd, J = 5.5, 2.6, 0.7 Hz, 2H), 2.68 (td, J = 2.5, 0.6 Hz, 1H).13C NMR (151 MHz, Acetone-d6) δ 165.5, 145.3, 141.3, 141.2, 138.3, 133.5, 129.9, 129.6, 128.9, 128.7, 126.3, 113.8, 80.9, 72.5. ESI-TOF (HRMS) m / z [M+H]+calculated for C19H16N3O3S 366.0907, found 366.0915. Attorney Docket No.: 3062 / 203 PCT 4-((4-(4-fluorophenyl)-1H-imidazol-1-yl)sulfonyl)-N-(prop-2-yn-1-yl)benzamide (Imyl- 04) Light yellow solid (80%, 120 mg)1H NMR (600 MHz, Acetone-d6) δ 8.36 (s, 1H), 8.31 – 8.28 (m, 1H), 8.24 (dq, J = 8.5, 1.9 Hz, 2H), 8.18 – 8.14 (m, 2H), 8.09 – 8.06 (m, 1H), 7.90 (ddd, J = 8.4, 5.4, 2.4 Hz, 2H), 7.15 (td, J = 8.9, 2.4 Hz, 2H), 4.19 (dt, J = 5.4, 2.6 Hz, 2H), 2.69 (q, J = 2.5 Hz, 1H).19F NMR (564 MHz, Acetone-d6) -115.60 (dqd, J = 11.1, 5.4, 2.1 Hz).13C NMR (151 MHz, Acetone-d6) δ 165.5, 163.5 (d, J = 245.1 Hz), 144.3, 141.2 (d, J = 24.4 Hz), 138.4, 129.9, 128.7, 128.3 (d, J = 8.2 Hz), 116.4 (d, J = 22.0 Hz), 113.6, 80.9, 72.5. ESI-TOF (HRMS) m / z [M+H]+calculated for C19H15FN3O3S 384.0813, found 384.0821. 4-((4-bromo-1H-imidazol-1-yl)sulfonyl)-N-(prop-2-yn-1-yl)benzamide (Imyl-Br) White solid (62%, 89.5 mg)1H NMR (600 MHz, Acetone-d6) δ 8.38 (s, 1H), 8.26 – 8.22 (m, 3H), 8.19 – 8.16 (m, 2H), 7.80 (dd, J = 1.6, 0.4 Hz, 1H), 4.21 (dd, J = 5.5, 2.5 Hz, 2H), 2.70 (t, J = 2.6 Hz, 1H).13C NMR (151 MHz, Acetone-d6) δ 165.4, 141.6, 140.5, 138.2, 130.0, 129.0, 119.5, 118.1, 80.9, 72.5. ESI-TOF (HRMS) m / z [M+H]+calculated for C13H11BrN3O3S 367.9699, found 367.9698. N-(prop-2-yn-1-yl)-4-((4-(trifluoromethyl)-1H-imidazol-1-yl)sulfonyl)benzamide (Imyl- TFM) Attorney Docket No.: 3062 / 203 PCT White solid (58%, 80.6 mg)1H NMR (600 MHz, Acetone-d6) δ 8.45 – 8.43 (m, 1H), 8.33 – 8.30 (m, 2H), 8.29 (p, J = 1.3 Hz, 1H), 8.21 – 8.18 (m, 2H), 4.23 – 4.18 (m, 2H), 2.70 (t, J = 2.6 Hz, 1H).19F NMR (564 MHz, Acetone-d6) δ -64.41.13C NMR (151 MHz, Acetone-d6) δ 165.3, 141.8, 140.2, 139.4, 130.1, 129.3, 122.0 (q, J = 267.0 Hz), 119.8 (q, J = 4.1 Hz), 80.9, 72.5. ESI-TOF (HRMS) m / z [M+H]+calculated for C14H11F3N3O3S 358.0468, found 358.0471. 3-methyl-1-((4-(prop-2-yn-1-ylcarbamoyl)phenyl)sulfonyl)-1H-imidazol-3-ium trifluoromethanesulfonate (Imyl-01+) White solid (55%, 40 mg)1H NMR (400 MHz, Acetone-d6) δ 9.83 (t, J = 1.5 Hz, 1H), 8.62 (d, J = 5.6 Hz, 1H), 8.47 – 8.42 (m, 2H), 8.34 (t, J = 2.0 Hz, 1H), 8.26 – 8.21 (m, 2H), 7.94 (d, J = 2.0 Hz, 1H), 4.22 – 4.17 (m, 2H), 2.68 (t, J = 2.5 Hz, 1H), 2.09 (s, 3H).13C NMR (201 MHz, Acetone-d6) δ 165.1, 165.0, 142.8, 138.7, 137.7, 130.5, 130.3, 127.4, 123.5, 121.3, 80.8, 72.4. ESI-TOF (HRMS) m / z [M+H]+calculated for C14H14N3O3S 304.0750, found 304.0758. 4-((1H-pyrazol-1-yl)sulfonyl)-N-(prop-2-yn-1-yl)benzamide (Py-01) White solid (70%, 79.5 mg)1H NMR (600 MHz, Acetone-d6) δ 8.35 (dt, J = 2.8, 0.5 Hz, 1H), 8.14 – 8.09 (m, 5H), 7.83 (dd, J = 1.6, 0.6 Hz, 1H), 6.57 (dd, J = 2.8, 1.6 Hz, 1H), 4.20 (dd, J = 5.5, 2.5 Hz, 2H), 2.70 (t, J = 2.5 Hz, 1H).13C NMR (151 MHz, Acetone-d6) δ 165.6, 146.8, 141.0, 140.5, 133.0, 129.5, 129.1, 110.4, 81.0, 72.4. ESI-TOF (HRMS) m / z [M+H]+calculated for C13H12N3O3S 290.0594, found 290.0595. 4-((3-phenyl-1H-pyrazol-1-yl)sulfonyl)-N-(prop-2-yn-1-yl)benzamide (Py-02) Attorney Docket No.: 3062 / 203 PCT White solid (78%, 111 mg)1H NMR (600 MHz, Acetone-d6) δ 8.41 (d, J = 2.9 Hz, 1H), 8.19 – 8.17 (m, 2H), 8.14 – 8.11 (m, 2H), 7.89 – 7.85 (m, 2H), 7.45 – 7.38 (m, 3H), 7.05 (d, J = 2.8 Hz, 1H), 4.20 – 4.17 (m, 2H), 2.68 (t, J = 2.6 Hz, 1H).13C NMR (151 MHz, Acetone-d6) δ 183.5, 165.6, 158.2, 141.0, 140.5, 134.6, 132.4, 130.4, 129.8, 129.5, 129.2, 127.2, 108.1, 81.0, 72.4. ESI-TOF (HRMS) m / z [M+H]+calculated for C19H16N3O3S 366.0907, found 366.0908. 4-((3-(4-methoxyphenyl)-1H-pyrazol-1-yl)sulfonyl)-N-(prop-2-yn-1-yl)benzamide (Py- White solid (71%, 110 mg)1H NMR (600 MHz, Acetone-d6) δ 8.36 (t, J = 2.9 Hz, 1H), 8.34 (s, 1H), 8.19 – 8.14 (m, 2H), 8.14 – 8.09 (m, 2H), 7.83 – 7.78 (m, 2H), 7.01 – 6.96 (m, 3H), 4.20 – 4.17 (m, 2H), 3.83 (s, 3H), 2.69 – 2.66 (m, 1H).13C NMR (151 MHz, Acetone-d6) δ 161.9, 158.1, 140.6, 134.6, 129.5, 129.1, 128.7, 124.9, 115.1, 107.9, 81.0, 72.4, 55.8. ESI-TOF (HRMS) m / z [M+H]+calculated for C20H18N3O4S 396.1013, found 396.1014. 4-((3-(4-fluorophenyl)-1H-pyrazol-1-yl)sulfonyl)-N-(prop-2-yn-1-yl)benzamide (Py-04) White solid (75%, 111 mg)1H NMR (600 MHz, Acetone-d6) δ 8.40 (ddd, J = 5.0, 3.2, 1.5 Hz, 1H), 8.34 (s, 1H), 8.17 (ddt, J = 6.0, 4.0, 1.9 Hz, 2H), 8.12 (dt, J = 6.7, 1.8 Hz, 2H), 7.91 (dddd, J = 7.7, 5.8, 3.9, 2.1 Hz, 2H), 7.20 (tdd, J = 9.1, 4.1, 2.0 Hz, 2H), 7.03 (ddd, J = 5.0, 3.1, 1.5 Hz, 1H), 4.18 (ddd, J = 4.8, 3.1, 1.6 Hz, 2H), 2.68 (dt, J = 3.4, 2.4 Hz, 1H).19F NMR (564 MHz, Acetone-d6) δ -113.49 – -113.60 (m).13C NMR (151 MHz, Acetone-d6) δ 183.5, 165.5 (d, J = 10.9 Hz), 164.4 (d, J = 246.7 Hz), 157.2, 141.0, 140.4, 134.8, 129.5, 129.4 (d, J = 8.4 Hz), 129.2, 116.6 (d, J = 21.9 Hz), 108.1, 80.9, 72.4. ESI-TOF (HRMS) m / z [M+H]+calculated for C19H15FN3O3S 384.0813, found 384.0814. Attorney Docket No.: 3062 / 203 PCT 4-((5-phenyl-2H-tetrazol-2-yl)sulfonyl)-N-(prop-2-yn-1-yl)benzamide (Tet-02) White solid (23%, 33.3 mg).1H NMR (600 MHz, Acetone-d6) δ 8.22 – 8.19 (m, 2H), 7.97 – 7.94 (m, 2H), 7.62 – 7.59 (m, 1H), 7.57 – 7.55 (m, 2H), 7.51 – 7.47 (m, 2H), 4.24 (d, J = 2.6 Hz, 2H), 2.71 (t, J = 2.5 Hz, 1H).13C NMR (151 MHz, Acetone-d6) δ 165.7, 155.6, 140.8, 140.6, 132.9, 130.7, 129.9, 129.7, 129.5, 81.1, 72.5. ESI-TOF (HRMS) m / z [M+H]+calculated for C17H14N5O3S+368.0812, found 368.0804. 4-((5-(4-methoxyphenyl)-2H-tetrazol-2-yl)sulfonyl)-N-(prop-2-yn-1-yl)benzamide (Tet- Light yellow solid (35%, 53.1 mg)1H NMR (600 MHz, Acetone-d6) δ 8.22 – 8.18 (m, 2H), 8.00 – 7.97 (m, 2H), 7.54 – 7.50 (m, 2H), 7.04 – 6.99 (m, 2H), 4.24 (d, J = 2.5 Hz, 2H), 3.89 (s, 3H), 2.71 (t, J = 2.6 Hz, 1H).13C NMR (151 MHz, Acetone-d6) δ 165.7, 163.9, 156.3, 140.9, 140.6, 131.7, 129.6, 129.4, 122.7, 114.9, 81.1, 72.4, 56.1. ESI-TOF (HRMS) m / z [M+H]+calculated for C18H16N5O4S+398.0918, found 398.0890. 4-((5-(4-fluorophenyl)-2H-tetrazol-2-yl)sulfonyl)-N-(prop-2-yn-1-yl)benzamide (Tet-04) Light yellow solid (25%, 37.3 mg)1H NMR (600 MHz, Acetone-d6) δ 8.21 (dt, J = 8.2, 0.5 Hz, 2H), 7.99 – 7.95 (m, 2H), 7.66 – 7.62 (m, 2H), 7.31 – 7.25 (m, 2H), 4.25 (dd, J = 4.6, 2.6 Attorney Docket No.: 3062 / 203 PCT Hz, 2H), 2.73 – 2.71 (m, 1H).19F NMR (564 MHz, Acetone-d6) δ -108.93 (tt, J = 8.7, 5.4 Hz).13C NMR (151 MHz, Acetone-d6) δ 167.1 (q, J = 250.7 Hz), 165.7, 165.6, 154.8, 140.9, 140.4, 132.4 (d, J = 9.1 Hz), 129.7, 129.6, 127.1, 116.6 (d, J = 22.4 Hz), 81.1, 72.5. ESI-TOF (HRMS) m / z [M+H]+calculated for C17H13FN5O3S+386.0718, found 386.0738. 1H-imidazol-1-yl 4-(prop-2-yn-1-ylcarbamoyl)benzenesulfonate (Imate-01) Procedure: 4-hydroxy-N-(prop-2-yn-1-yl)benzamide (353 mg, 2.02 mmol) was dissolved in acetone (10 mL, 0.2 M) and stirred.1,1’-Sulfonyldiimidazole (398 mg, 2.02 mmol) and cesium carbonate (658 mg, 2.02 mmol) were added and the reaction stirred at room temperature overnight. The reaction was adsorbed onto Celite and concentrated in vacuo. The product was purified by silica gel flash chromatography (10-50% gradient ethyl acetate in hexanes) affording the product as a white solid (90%, 556 mg).1H NMR (600 MHz, Chloroform-d) δ 7.84 – 7.78 (m, 2H), 7.74 (t, J = 1.1 Hz, 1H), 7.29 (t, J = 1.5 Hz, 1H), 7.15 (dd, J = 1.6, 0.8 Hz, 1H), 7.02 – 6.96 (m, 2H), 6.84 (t, J = 5.2 Hz, 1H), 4.20 (dd, J = 5.2, 2.5 Hz, 2H), 2.26 (t, J = 2.6 Hz, 1H).13C NMR (151 MHz, Chloroform-d) δ 165.6, 151.1, 137.5, 134.4, 131.5, 129.6, 121.8, 118.5, 79.2, 72.2, 30.0. ESI-TOF (HRMS) m / z [M+H]+calculated for C13H12N3O4S+306.0543, found 306.0545. 4-bromo-1-((4’-methoxy-[1,1’-biphenyl]-4-yl)sulfonyl)-1H-imidazole (KY-2) White solid (80%, 226.4 mg) 1H NMR (600 MHz, Chloroform-d) δ 7.98 – 7.95 (m, 2H), 7.75 – 7.72 (m, 2H), 7.56 – 7.52 (m, 2H), 7.30 (d, J = 1.5 Hz, 1H), 7.04 – 6.99 (m, 2H), 3.87 (s, 3H).13C NMR (151 MHz, Chloroform-d) δ 160.8, 148.2, 136.4, 134.8, 130.8, 128.8, 128.2, 128.0, 118.8, 116.6, 114.9, 55.6. ESI-TOF (HRMS) m / z [M+H]+calculated for C16H14BrN2O3S+392.9903, found 392.9907. Attorney Docket No.: 3062 / 203 PCT 4-bromo-1-((4-methoxyphenyl)sulfonyl)-1H-imidazole (KY-342) White solid (85%, 269.6 mg)1H NMR (600 MHz, Chloroform-d) 7.90 – 7.86 (m, 3H), 7.25 (d, J = 1.6 Hz, 1H), 7.05 – 7.01 (m, 2H), 3.89 (s, 3H).13C NMR (201 MHz, Chloroform-d) δ 165.2, 136.3, 130.2, 128.4, 116.5, 115.4, 56.1. ESI-TOF (HRMS) m / z [M+H]+calculated for C10H10BrN2O3S+316.9590, found 316.9599. 4-bromo-1-(cyclopropylsulfonyl)-1H-imidazole (KY-5) White semi-solid (50%, 874 mg)1H NMR (600 MHz, Chloroform-d) δ 8.00 (d, J = 1.1 Hz, 1H), 7.82 (d, J = 1.6 Hz, 0H), 7.28 (d, J = 1.5 Hz, 0H), 7.11 (d, J = 1.1 Hz, 1H), 2.93 (tt, J = 7.9, 4.7 Hz, 1H), 2.66 (tt, J = 7.9, 4.7 Hz, 0H), 1.55 – 1.50 (m, 2H), 1.49 – 1.44 (m, 1H), 1.30 – 1.23 (m, 3H).13C NMR (201 MHz, Chloroform-d) δ 139.3, 136.5, 133.5, 118.6, 116.8, 33.0, 32.9, 7.8, 7.8. ESI-TOF (HRMS) m / z [M+H]+calculated for C6H8BrN2O2S+250.9484, found 250.9489. 1-((4-methoxyphenyl)sulfonyl)-4-(trifluoromethyl)-1H-imidazole (KY-6) White solid (85%, 262 mg)1H NMR (600 MHz, Chloroform-d) δ 8.02 (s, 1H), 7.94 – 7.90 (m, 2H), 7.60 (p, J = 1.3 Hz, 1H), 7.07 – 7.03 (m, 2H), 3.90 (s, 3H).19F NMR (564 MHz, Chloroform-d) -63.87..13C NMR (201 MHz, Chloroform-d) δ 165.4, 137.3, 134.6 (d, J = 39.7 Hz), 130.4, 128.0, 120.6 (q, J = 268.1 Hz), 117.5 (q, J = 3.9 Hz), 115.6, 56.2. ESI-TOF (HRMS) m / z [M+H]+calculated for C11H10F3N2O3S+307.0359, found 307.0368. Attorney Docket No.: 3062 / 203 PCT (4-(2-methoxyphenyl)piperazin-1-yl)(3-((3-(pyridin-3-yl)-1H-1,2,4-triazol-1-yl)sulfonyl)- phenyl)methanone (RJG-2096) White solid (83%, 248 mg)1H NMR (497 MHz, cdcl3) δ 9.31 (d, J = 2.2 Hz, 1H), 8.79 (d, J = 1.2 Hz, 1H), 8.66 (dd, J = 4.7, 1.6 Hz, 1H), 8.34 (dd, J = 7.8, 2.2 Hz, 1H), 8.21 (dd, J = 7.8, 1.3 Hz, 2H), 7.82 (dt, J = 7.7, 1.3 Hz, 1H), 7.74 – 7.67 (m, 1H), 7.33 (dd, J = 8.0, 4.9 Hz, 1H), 7.08 – 7.03 (m, 1H), 6.98 – 6.87 (m, 4H), 3.98 (s, 2H), 3.86 (s, 3H), 3.55 (s, 2H), 3.16 (s, 2H), 3.00 (s, 2H).13C NMR (126 MHz, Acetone-d6) δ 167.7, 163.7, 153.5, 152.4, 148.7, 148.1, 142.0, 139.3, 137.2, 135.3, 134.8, 131.4, 130.2, 128.1, 126.2, 124.7, 124.0, 121.8, 119.3, 112.8, 55.8. ESI-TOF (HRMS) m / z [M+H]+calculated for C25H25N6O4S+505.1653, found 505.1652. (4-(2-methoxyphenyl)piperazin-1-yl)(3-((4-(pyridin-3-yl)-1H-imidazol-1-yl)sulfonyl)- phenyl)methanone White solid (74%, 514 mg).1H NMR (600 MHz, acetone-d6) δ 8.58 – 8.54 (m, 2H), 8.41 (dd, J = 10.2, 1.3 Hz, 2H), 8.25 (ddd, J = 8.0, 2.0, 1.1 Hz, 1H), 8.21 (t, J = 1.8 Hz, 1H), 7.90 (dt, J = 7.7, 1.4 Hz, 1H), 7.83 (t, J = 7.8 Hz, 1H), 7.81 – 7.79 (m, 2H), 7.00 – 6.93 (m, 2H), 6.91 – 6.88 (m, 2H), 3.82 (s, 4H), 3.49 (s, 2H), 3.10 (s, 2H), 2.97 (s, 1H), 2.79 (d, J = 18.1 Hz, 9H).13C NMR (201 MHz, acetone-d6) δ 167.7, 153.5, 151.2, 142.6, 142.0, 140.5, 139.4, 139.0, 138.7, 134.7, 131.4, 129.2, 127.1, 123.9, 121.8, 120.3, 119.2, 116.6, 112.8, 55.8. ESI-TOF (HRMS) m / z [M+H]+calculated for C26H26N5O4S+504.1700, found 504.1701. Attorney Docket No.: 3062 / 203 PCT (4-(2-methoxyphenyl)piperazin-1-yl)(3-((4-(pyridin-4-yl)-1H-imidazol-1-yl)sulfonyl)- phenyl)methanone (RJG-3017) White solid (68%, 472 mg)1H NMR (600 MHz, acetone-d6) δ 9.07 (dd, J = 2.3, 0.9 Hz, 1H), 8.48 (dd, J = 4.8, 1.7 Hz, 1H), 8.38 (d, J = 1.3 Hz, 1H), 8.28 (d, J = 1.3 Hz, 1H), 8.24 (ddd, J = 7.9, 2.0, 1.1 Hz, 1H), 8.21 (t, J = 1.8 Hz, 1H), 8.18 (dt, J = 8.0, 2.0 Hz, 1H), 7.90 (dt, J = 7.7, 1.3 Hz, 1H), 7.83 (t, J = 7.8 Hz, 1H), 7.36 (ddd, J = 7.9, 4.8, 0.9 Hz, 1H), 6.98 (ddd, J = 8.5, 6.1, 2.6 Hz, 1H), 6.96 – 6.93 (m, 1H), 6.90 – 6.87 (m, 2H), 3.83 (s, 5H), 3.50 (s, 2H), 3.03 (m, 4H).13C NMR (201 MHz, acetone-d6) δ 167.7, 153.5, 149.8, 147.6, 142.3, 142.0, 139.4, 139.1, 138.7, 134.6, 133.1, 1314., 129.2, 129.1, 127.0, 124.4, 123.9, 121.8, 119.3, 114.8, 112.8, 55.8. ESI-TOF (HRMS) m / z [M+H]+calculated for C26H26N5O4S+504.1700, found 504.1695. HPLC assay for profiling solution reactivity of sulfonyl probes. The following reagents were prepared and stored on ice prior to use. 0.1 M solution of caffeine in MeCN, 1.0 M solution of n-butylamine, p-cresol, tetramethylguanidine (TMG), 1 M HOAc in MeCN and 10 mM solution of SuTEx fragment in DMF-MeCN mixture (10:90, v / v).500 μL of a fragment solution was transferred to a dram vial on ice. To the mixture, 5.5 μL of TMG and 5.5 μL of p- cresol or n-butylamine were added and solutions were stirred on ice for 6 hr. To monitor reactivity, 50 μL aliquots were removed at indicated time points and quenched with 10 μL of a 1:1 mixture of caffeine and HOAc solutions described above. Samples were injected (1 μL) and analyzed by reverse-phase HPLC on a Shimadzu 1100 Series spectrometer with UV detection at 254 nm. Chromatographic separation was performed using a Phenomenex Kinetex C18 column (2.6 μm, 50 x 4.6 mm). Mobile phases A and B were composed of H2O + 0.1% HOAc and MeCN + 0.1% HOAc, respectively. Samples were analyzed using the following analytical conditions: using a flow rate of 0.8 mL min−1, the gradient was as follows: 0– 0.5 min, 15% B; 0.5–6.5 min 85% B; 6.5–7 min 100% B; 7–8.5 min 100% B; 208.5–9 min 15% B; 9–9.8 min 15% B. Reaction progress was evaluated by monitoring consumption of starting material (SufAz compound) normalized to caffeine standard. The amount of starting material consumed was calculated using the area under the curve (AUC) for the fragment peak Attorney Docket No.: 3062 / 203 PCT at time (t) = experimental / t = 0. All SufAz compound peak AUCs used for calculations were normalized to caffeine standard AUCs at respective time points to account for run-to-run variations by HPLC. The amount of SufAz compound consumed (% starting material) was plotted as a function of time and the half-life for consumption was calculated by non-linear regression (one phase decay) in GraphPad Prism. EXAMPLE 2 Biological Methods SILAC cell culture. SILAC cells were cultured at 37 °C with 5% CO2 in either ‘light’ or ‘heavy’ media supplemented with 10% dialyzed fetal bovine serum (Omega Scientific), 1% L-glutamine (Fisher Scientific), and isotopically labeled amino acids. Light media was supplemented with 100 μg mL−1 L-arginine and 100 μg mL−1 L-lysine. Heavy media was supplemented with 100 μg mL−1 [13C615N4] L-arginine and 100 μg mL−1 [13C615N2] L-lysine. Cell were grown in SILAC media for at least five passages before utilizing SILAC cells for experiments. Transient transfection. Recombinant proteins were produced by transient transfection of HEK293T as previously described in Brulet et al., 2020. pcDNA3.1-PTGR2-FLAG was purchased from GenScript. PTGR2 biochemical assay. Soluble fractions of mock and overexpressed PTGR2 HEK293T proteome (0.22 mg) were incubated with vehicle or compound for 30 min at 37 ⁰C. The reaction mixture containing NADPH (1.1 mM), DTT (1.1 mM), EDTA (1.1 mM), and 15- keto-PGE2 (0.022 mM) was added to samples. The mixture was incubated at for 2 hours at 37 ⁰C. The reaction was quenched by addition of 335 µL of 2:1 chloroform:methanol with 50 µg / mL BHT, and 15-keto-PGE2-d4 (2.5 nmol). Samples were vortexed and chilled on ice for 5 min. The organic and aqueous layer were separated via centrifugation at 2,000 x g for 4 min. The organic layer was then collected, dried under nitrogen, and resuspended in 100 µL of 1:1 mixture of methanol and IPA. Microflow-electrospray ionization–LC–MS / MS analyses were performed using a TSQ Quantis Plus Triple Quadrupole Mass Spectrometer. 1 µL of sample was injected, and the following LC conditions were used on the Vanquish Neo UHPLC System with a Thermo Fisher C18200 µm x 2.0 cm column held at 40 ⁰C. LC conditions (A: 5% IPA, 95% H2O, 0.1% acetic acid; B: 40% ACN, 40% IPA, 20% H2O, 0.1% acetic acid) used the following gradient with a constant flowrate of 80 µL / min: 0-0.5 min 45% B, 0.5-2.5 min 99% B, 2.5-4.0 min 99% B, 4.0-4.1 min 45% B. Instrument was operated in negative ion mode, and the following Attorney Docket No.: 3062 / 203 PCT transitions were acquired. 15K-PGE2: 349.133 »112.967, 349.133 »160.967, 349.133 »172.967, 349.133 »234.967, 349.133 »287.050. 13,14-DH-15K-PGE2: 351.050 » 112.967, 351.050 » 174.967, 351.050 » 203.883, 351.050 » 235.050, 351.050 » 315.05.15K-PGE2-d4: 353.133 »163.976, 353.133 »192.967, 353.133 »226.967, 353.133 » 238.967, 353.133 »291.133. GST Activity Assay. PDAC608T soluble cell proteomes were diluted to 0.25 mg / ml in assay buffer (100 mM NaH2PO4, pH 7.0) and 25 µL was added to each well of a 96 well plate. Compound stock solutions were diluted in DMSO and 1 µL of 25X stock solution was added to respective wells and incubated for 1 hr at 37 °C. GSH stock solution (250 mM in water) was diluted to 4 mM in assay buffer and 25 µl of diluted GSH solution was added to each sample. A substrate stock solution of 75 mM 1-chloro-2,4-dinitrobenzene (CDNB) in ethanol was diluted to 2 mM in assay buffer. Then, 50 µl of 2 mM CDNB was added to each well and the absorbance was measured at 340 nm after 60 min of reaction time on a BMG Labtech CLARIOstar plate reader. SILAC Sample Preparation, Data Acquisition, and Analysis. Probe modified proteome was prepared as previously described in Brulet et al., 2020; Toroitich et al., 2021. Heavy and light SuTEx modified peptides were analyzed on a Thermo Fisher Q-Exactive Plus coupled to an Ultimate 3000 RSLC nanoSystem using previously described acquisition parameters. See Brulet et al., 2020; Toroitich et al., 2021. Peptide identification and quantification was accomplished with the BYONIC™ software package (Protein Metrics Inc.) using protocols and quality control metrics described in Ciancone et al., 2023. Sample preparation for tandem mass tag (TMT) LC-MS / MS chemical proteomics. Aliquots of Colo 205 proteome (1 mg) were incubated with 250 µM ligand or DMSO (1 hr, 37 ⁰C) and then treated with 250 µM HHS-465 (1 hr, RT). Desthiobiotin-azide was conjugated to the probe modified proteome using CuAAC and chloroform methanol extractions were used to remove click reagents as described in Ciancone et al., 2023. Following resuspension in 6 M Urea / 25 mM AmBic, proteins were reduced by dithiothreitol and alkylated with iodoacetamide as described in Fox, 1943; Polgar, 2005; Agback & Agback, 2018; Moro et al., 2020. Denaturing reagents were removed via chloroform methanol extraction. Proteins were digested overnight with Tryp-Lys-C in 25mM AmBic (7.5 µg, 37 °C). The resulting peptides were desalted for TMT labeling using PIERCE™ Peptide Desalting Spin Columns. TMT labeling. Peptide concentrations were normalized to 5 µg / µL in EPPS (pH 8.5) using the PIERCE™ Quantitative Colorimetric Peptide Assay. Purified SuTEx-modified BSA Attorney Docket No.: 3062 / 203 PCT peptides were added to each condition prior to TMT labeling as a chemoproteomic standard to normalize for sample enrichment and cleanup. TMTSIXPLEX™ was used to isotopically label 50 µg of peptide per channel at a 2:1 w / w ratio of label to peptide (1 hour, room temperature (RT), 500 rpm shaking). The TMT reaction was quenched with 6% hydroxylamine (15 minutes, RT) and channels were mixed 1:1. Samples were dried using a speed vac and reconstituted in 500 µL DPBS. Streptavidin enrichment of modified peptides. SuTEx modified peptides were enriched with avidin agarose and eluted using 150 µL of 50% ACN + 0.1% formic acid (3X) as described in Ciancone et al., 2023. Enriched peptides were dried, resuspended in 25 µL 0.1% formic acid, and stored at -80 ⁰C until analysis. LC-MS / MS evaluation of TMT-tagged SuTEx-modified peptides. Peptides were analyzed with nano-electrospray ionization-liquid chromatography-mass spectrometry (LC- MS / MS) on a Vanquish Neo UHPLC (Thermo) coupled to an Orbitrap Eclipse Tribrid mass spectrometer. Peptides were separated an 85 min gradient by reverse phase LC using 3 µm C18 (20 cm) as follows: (A: 0.1% formic acid / H2O; B: 80% ACN, 0.1% formic acid in H2O): 0– 2 min 4% B, 450 nL / min; 2–4 min 4.5% B, 450 nL / min; 4–24 min 20% B, 300 nL / min; 24–74 30% B, 300 nL / min; 74–79 min 45% B, 300 nL / min; 79–81 min 50% B, 300 nL / min; 81– 83.5 min 99% B, 450 nL / min; 83.5–85 min 99% B, 450 nL / min. Data was acquired using a top 30 ddMS2 method. MS1 spectra were acquired at 120K resolution with a maximum injection time of 20 ms and MS2 spectra were taken with an AGC of 25K, quadrupole isolation width of 0.7m / z, and max IT of 75 ms. LC-MS / MS data analysis for TMT-tagged SuTEx modified peptides. Peptide identification and quantification was accomplished with Proteome Discoverer 3.0 and a PMI- Byonic node. MS2 spectra were searched against the human protein database (Uniprot, download date 01 / 17 / 2024) using the following parameters: ≤2 missed cleavages, 10 ppm precursor mass tolerance, 20 ppm fragment mass tolerance, and 1% protein false discovery rate. Modifications considered included SuTEx (+635.2737, Y, K, variable), methionine oxidation (+15.9949, M, variable), cysteine carbamidomethylation (+57.021464, C, fixed), and TMT modification (+229.1629, N-term, K, variable. Peptides used for quantification met the following quality control criteria: PMI-Byonic Score ≥300, delta ppm err. 5, co-isolation interference threshold ≤ 50%, reporter ion S / N ≥10, and were present in n=2 biological replicates. TMT channels were normalized to SuTEx-BSA chemoproteomic peptide standard. Volcano plots were generated by grouping PSMs using the peptide isoform node with cutoffs Attorney Docket No.: 3062 / 203 PCT of Log2 FC≥0.5, and p-value ≤0.05. For sites of interest, a median ratio was calculated from all isoforms adducted at the same position. EXAMPLE 3 Synthesis of Sulfonyl- Azoles Sulfonyl-azole (SufAz) probes were synthesized by (i) coupling propargylamine to 4- (chlorosulfonyl) benzoyl chloride followed by (ii) nucleophilic substitution by the azole to yield the alkyne-modified SufAz (sulfonyl-tetrazole, -pyrazole, and -imidazole) probes. See Figures 1A and 1B. The alkyne handle provides for detection of probe-modified sites in chemoproteomic workflows as described in Brulet et al., 2020; Toroitich et al., 2021. The imidazole sulfonate probe (Imate-01) was synthesized in a similar fashion where 1,1’- sulfonyldiimidazole was coupled with 4-hydroxy-N-(prop-2-yn-1-yl) benzamide and purified via silica gel flash chromatography. See Figures 1A and 1B. To determine whether the reactivity of SufAz probes could be modulated, analogs bearing electron-withdrawing (EWG) and -donating (EDG) elements on the heterocyclic group were synthesized. Methylation of the imidazole using methyl trifluoromethanesulfonate could increase the LG ability of this heterocycle. This activated counterpart was designated Imyl-01+. See Figure 1B. EXAMPLE 4 HPLC Reactivity Analyses of SufAz Probes Reactivity of SufAz probes was initially evaluated in solution against nucleophiles using a high-performance liquid chromatography (HPLC) assay as described in Brulet et al., 2020. See Figures 2A and 2B. A series of nucleophiles was selected for evaluation to mimic side chains of amino acids in proteins: p-cresol (tyrosine), n-butylamine (lysine), n-butanethiol (cysteine), butyric acid (aspartic / glutamic acid) and propionamide (glutamine / asparagine). The reaction was initiated by addition of 1,1,3,3-tetramethylguanidine (TMG) base and progress was monitored at set timepoints by quantifying the area under the curves (AUC) of probe consumption. See Figures 2B and 7. First, the LG ability of imidazole was evaluated for reaction of Imyl-01 with various nucleophiles. Imyl-01 was mostly consumed after 6 hours of reaction time with p-cresol, whereas only ~50% and ~15% consumption was observed with butanethiol and n-butylamine mimetics, respectively. See Figure 2C. A phenyl substitution on the imidazole (Imyl-02) did not have a significant effect on reactivity compared with Imyl-01 (t1 / 2 ≈ 100 min), and both Imyl-01 and Imyl-02 were overall less reactive than the sulfonyl-triazole (SuTEx; Brulet et al., 2020) congener HHS-481 (t1 / 2= 1.1 min). See Figures 1B and 2D. Py-02 and Tet-02 were Attorney Docket No.: 3062 / 203 PCT largely inert under the reaction conditions against both p-cresol and n-butylamine. See Figures 2D and Figure 8, respectively. Next, the imidazole was modified to alter LG ability in order to assess whether reactivity of sulfonyl-imidazoles was tunable. Installing EWGs on the imidazole increased the reactivity of Imyl probes with p-cresol. A 4-fluorophenyl substitution (Imyl-04) resulted in a slight increase in reactivity; however, addition of an EWG directly to the imidazole, such as a 4-bromoimidazole (Imyl-Br) or 4-trifluoromethylimidazole (Imyl-TFM), significantly increased reactivity. See Figure 2E. Rapid reaction of Imyl-01+ was observed with n- butylamine and p-cresol, which supports the imidazolium functioning as a highly activated nucleofuge. These findings are generally in agreement with previous reports of arylsulfonyl imidazolium triflates as effective sulfonating reagents for preparing sulfonamides and sulfonates. See Monjoint & Ruasse, 1984; Robinson et al., 1998; O'Connell & Rapoport, 2002; Pearson et al., 2002; Anderson & Whiting, 2003; Reyes-Rangel, et al., 2016. Imyl-01+ appeared to react rapidly with all nucleophiles tested and could have potential stability issues in solvent due to general hydrolysis (t1 / 2 < 1 min). See Figure 9A. The reactivity of sulfonyl (Imyl-01)- and sulfonate (Imate-01)-imidazole probes was compared by HPLC and it was found that Imate-01 was largely inert under the reaction conditions tested. See Figure 9B. EXAMPLE 5 Chemical Proteomic Evaluation of SufAz Probes To evaluate activity of SufAz probes at protein sites, HEK293T cell lysates were treated with compounds (100 µM, 37 ºC, 30 min) followed by copper-catalyzed azide-alkyne cycloaddition (CuAAC) with a rhodamine-azide fluorescent tag and SDS-PAGE analysis. Differences in probe reactivity were assessed by comparing intensity of fluorescent protein bands detected. Results from SDS-PAGE were largely consistent with the HPLC assay results described above. Probes containing a pyrazole or tetrazole LG (Py and Tet analogs) were relatively inert in the proteome. In contrast, Imyl-01 showed enhanced activity compared with Imyl-02 and Imyl-04. See Figure 3A. Compared to HHS-475, Imyl-01 binding activity was dramatically lower in HEK293T, Jurkat, and DM93 lysate. See Figure 10. Both Imate-01 and Imyl-01+ showed minor activity and, without being bound to any one theory, the lack of activity for the latter is likely due to hydrolysis of the sulfonyl-imidazolium electrophile in aqueous conditions. See Figure 3B. The imidazole LGs modified with EWGs such as a 4- Attorney Docket No.: 3062 / 203 PCT bromo (Imyl-Br) or 4-trifluoromethyl (Imyl-TFM) showed augmented binding activity with evidence for tunable binding to proteins in lysates. See Figures 3B and 11. To determine if Imyl probes are cell permeable, DM93 cells were treated with Imyl-01 at various time points (25 µM, 10 – 120 min) and time dependent protein labeling was observed with the highest fluorescent probe labeling at 2 hours using gel-based chemical proteomics. See Figure 12. Cellular treatment studies were expanded to additional Imyl analogs (100 µM, 37 ºC, 120 min) in HEK293T cells and the in situ labeling profiles were comparable with the lysate evaluations, providing evidence for cell permeability and further corroborated the tunable nature of this electrophile. See Figure 3C. Based on the collective data, sulfonyl- imidazoles were determined to be more suitable for chemoproteomic applications because of the tunable nature of this scaffold for covalent binding to proteins in lysates and live cells. EXAMPLE 6 Arylsulfonyl Imidazoles are Tempered Tyrosine- and Lysine-reactive Probes in Cells Liquid chromatography-mass spectrometry (LC-MS / MS) chemical proteomics was performed to identify the target proteins and binding sites of Imyl-01 and the 4-substituted counterparts. SILAC light and heavy DM93 cells were differentially treated with DMSO or Imyl probes in situ (100 μM, 2 hrs, 37 °C). After treatment, cells were harvested, washed, and fractionated to yield the soluble proteome that subsequently underwent CuAAC conjugation with a desthiobiotin-PEG3azide tag. The tagged proteins were digested with trypsin and probe- modified peptides were enriched by avidin affinity chromatography, eluted, and analyzed by LC-MS / MS as described in Brulet et al., 2020; Toroitich et al., 2021. See Figures 4A and 4B. High quality probe-modified peptides were identified using quality control criteria that included a 1% protein false discovery rate (FDR), Byonic score ≥ 300, and ≤5 ppm mass accuracy. See Brulet et al., 2020; Toroitich et al., 2021. For the imidazole probes, probe modification occurred principally on tyrosine (Y) and lysine (K) residues, with 583 tyrosine and 289 lysine sites (corresponding to 439 total proteins) reliably quantified (SILAC ratio or SR >5) across at least 2 replicates (n ≥ 2) of each probe treatment. Proteome coverage by Imyl- probes was variable. The Imyl-TFM probe showed highest apparent reactivity (545 distinct probe-modified sites; 419 sites unique to Imyl-TFM). Imyl-01 was less reactive than Imyl-TFM, resulting in 393 probe-modified sites with >70% of these sites unique to Imyl-01. Imyl-Br showed tempered reactivity with only 82 modified sites that largely overlapped with Imyl-01- and Imyl-TFM-modified sites. See Figure 4C. The proteomic reactivity of Imyl-02 and Imyl-04 was drastically reduced with no detectable sites Attorney Docket No.: 3062 / 203 PCT for Imyl-02 and only a single probe-modified site for Imyl-04 that meet our quality control criteria probe. A large fraction of Imyl probe-modified sites (>85%) overlapped with sites detected by sulfonyl-triazole probes in treated cells (aggregate sites from HHS-475 and HHS- 481 treatments in DM93 cells, 100 µM, 2 hrs. See Figures 4D. The chemoselectivity for tyrosine (Y) versus lysine (K) modification from cellular labeling studies was variable across the Imyl probes tested. Imyl-01 exhibited a modest preference for modification of lysine over tyrosine (Y / K ratio of <1). See Figure 4E. Imyl-TFM and Imyl-Br were more akin to chemoselectivity of SuTEx probes and preferentially modified tyrosines (Y / K ratio >4). Imyl-TFM displayed the highest chemoselectivity towards tyrosine while maintaining good proteome-wide coverage. See Figures 4C and 4E. EXAMPLE 7 Proteome-wide Evaluation of Imyl Ligands Next, a series of Imyl ligand compounds were synthesized to evaluate whether this sulfone-based electrophile can be used as ligands for targeting protein sites. The probe binding studies demonstrated high and low reactivity for the TFM- and Br-imidazole LGs, respectively. See Figure 4C. Imyl ligands were prepared bearing these modified imidazole LGs in conjunction with varying adduct group modifications and their ability to ligand sites was assessed. See Figure 5A. First, the chemical reactivities of the Imyl ligands was tested by HPLC. The cyclopropyl-modified Imyl compound KY-5 did not react appreciably with p- cresol or n-butylamine. KY-2, modified with the same LG but different AG, displayed moderate activity against p-cresol (t1 / 2 = 25 min) and low activity against n-butylamine. Both KY-342 and KY-6 showed high activity towards p-cresol while only the latter compound also showed a similar reactivity towards n-butylamine (t1 / 2< 5 min). See Figure 5B. Next, LC-MS / MS chemical proteomics was performed to identify protein sites liganded by the Imyl fragment compounds evaluated in the HPLC studies. A 6-plex tandem mass tag (TMT) chemical proteomics workflow was used for quantitative and multiplexed evaluation of probe-modified sites competed by Imyl ligand pretreatment. TMT achieves isotopic labeling at the peptide level using isotopically labeled, amine-reactive reagents that can be combined in a highly multiplexed fashion to yield an isobaric peptide MS1 mass and 6 unique MS2 reporter fragment ions for simultaneous quantitation by LC-MS / MS (Rauniyar & Yates, 3rd, 2014; Mertins et al., 2018. Since Imyl and SuTEx probes principally modify Y and K sites, a broad spectrum SuTEx probe was used for evaluating Imyl ligand compound activity. See Figure 13 for experimental details of the TMT SuTEx method. Attorney Docket No.: 3062 / 203 PCT Colo 205 soluble and membrane proteomes were pretreated with Imyl compounds (250 µM, 1 hr) followed by labeling with the broad-reactive SuTEx probe HHS-465 (Ciancone et al., 2023) under comparable labeling conditions. Proteomes were subjected to CuAAC with desthiobiotin-azide, proteolytically digested with trypsin protease, and isotopically labeled with amine-reactive TMT reagents (6-plex). Afterwards, desthiobiotinylated peptides were enriched and subjected to LC-MS / MS analysis as described in Ciancone et al., 2023. In total, >9,300 probe-modified sites were detected across ~2,400 proteins from aggregate membrane and soluble proteome datasets using TMT-SuTEx. Probe- and TMT-modified peptides used for quantitation were selected based on quality control metrics including Byonic score (>300) and mass accuracy (≤5 ppm). Proteome-wide coverage using TMT-SuTEx was comparable to previous studies using SILAC (Ciancone et al., 2023) with the added benefit of high multiplexing that enabled simultaneous comparison of Imyl ligand binding activity in a single mixed sample. If reproducibly liganded sites were considered (competition ratio or CR <0.5 for inhibitor / DMSO vehicle comparisons across 2 biological replicates), the Imyl ligand compounds, in general, displayed a restricted binding profile compared with the SuTEx ligand JWB198 tested at a 10- fold lower concentration. See Figures 5C, 14A, and 14B. The tempered protein binding activity of Imyl ligand compounds were more akin to the reactivity of aryl fluorosulfates (Mortenson et al., 2018) when directly compared to sulfonyl-triazole counterparts. See Brulet et al., 2020. Proteins reproducibly and significantly liganded by Imyl ligand compounds included enzymes, adaptor proteins, and helicase proteins in soluble proteomes although a small number of binding events were detected in membrane fractions (log2competition ratio or CR <0.5 for Imyl fragment / DMSO vehicle, p <0.05). See Figures 5C and 14A. Notable targets of KY-2 and KY-6 include aldo-keto reductase family 1 member C1 (AKR1C1 at Y24 and Y55) and 14-3- 3-zeta (YWHAZ at Y211). Prominent binding of KY-342 to aldehyde dehydrogenase 3 family member A1 (ALDH3A1 Y305) was observed. See Figure 5C. Akin to sulfonyl-triazoles, a cyclopropyl modification on the AG reduced binding activity; KY-5 displayed very minor to negligible binding activity in both soluble and membrane proteomes evaluated. See Figures 5C and 14A. EXAMPLE 8 Development of a Sulfonyl-imidazole GST and PTGR2 Inhibitor The restricted binding profiles of Imyl ligands suggested that the imidazole LG could be leveraged for improving selectivity of covalent inhibitors. Covalent inhibitors of Attorney Docket No.: 3062 / 203 PCT prostaglandin reductase 2 (PTGR2), a lipid enzyme that catalyzes the NADPH-dependent reduction of 15-keto-PGE2 to produce 13,14-dihydro-15-keto-PGE2 (Toroitich et al., 2021), were recently reported. From this series, a lead 1,2,4-sulfonyl-triazole inhibitor RJG-2096 was identified that blocked PTGR2 biochemical activity with moderate potency as determined by a LC-MS substrate assay (IC50 of ~960 nM). See Figures 6A-6C. Herein, substitution of the triazole for an imidazole LG counterpart in the RJG-2096 scaffold was studied to see if the resulting imidazole-containing ligand (i) could retain PTGR2 inhibitory activity, and (ii) improve selectivity against targets commonly bound by SuTEx compounds including glutathione S-transferase (GST) enzymes. See Mortenson et al., 2018; Brulet et al., 2020. RJG-3016 and RJG-3017 were synthesized. These compounds retain the AG binding element but differed from RJG-2096 via incorporation of a substituted imidazole LG. See Figure 6A. The PTGR2 inhibitory activities of these Imyl compounds were evaluated by LC- MS substrate assay. Considerably increased production of 13,14-dihydro-15-keto-PGE2was observed in PTGR2 overexpressed compared with mock transfected HEK293T proteomes exposed to 15-keto-PGE2 substrate. See Figures 6B and 15. Pretreatment with RJG-3017 resulted in concentration-dependent blockade of recombinant PTGR2 activity with equipotency compared to RJG-2096 (IC50values of ~900 nM for Imyl and SuTEx inhibitors). See Figure 6C. Interestingly, the 3-pyridyl substituted Imyl inhibitor (RJG-3016) showed substantially reduced inhibitory activity. Both RJG-3016 and -3017 showed reduced activity against endogenous GST enzymes detected in cell proteomes using a reported biochemical substrate assay (Brulet et al., 2020). See Figure 6D. These results support imidazole as an effective LG for developing covalent inhibitors with good potency and reduced activity against targets commonly bound by sulfone-based electrophiles. Discussion of the EXAMPLES Activity-based protein profiling (ABPP) is a powerful technique used to covalently modify functional sites in the proteome. The use of sulfur-triazole exchange (SuTEx) chemistry to study tyrosine and lysine sites on proteins using sulfonyl-triazole electrophiles. See Ciancone et al., 2023. The ability of SuTEx to modify tyrosines has provided for the discovery of hyper- reactive tyrosines (i.e. increased nucleophilicity due to the local protein environment) as well as pervanadate sensitive phosphorylation sites. See Brulet et al., 2020. Altering the electronics of the LG (e.g., by modifying the 1,2,4-triazole group) modulated the number of probe- modified sites and the Y / K ratio detected by LC-MS / MS chemical proteomics. See Brulet et al., 2020. Attorney Docket No.: 3062 / 203 PCT Further studies were undertaken to determine if altering the heterocyclic nucleofuge itself would produce a proportional alteration to accessible binding sites and amino acid preference due to the various pKas of the azoles. The innate reactivity of alternative azole analogs (e.g., pyrazole, imidazole, imidazolium, and tetrazole) was studied and it was found that the imidazole-based LGs provided a tunable scaffold for chemoproteomics. See Figures 3A-3C. For example, addition of a strong electron-withdrawing trifluoromethyl group to the LG of Imyl compounds facilitated rapid reaction with p-cresol whereas the unsubstituted imidazole analog Imyl-01 was significantly less reactive both in solution and proteomes. See Figures 2A-2E and 4A-4E. The reactivity of SufAz probes (Py-02, Imyl-02, Tet-02, and HHS-481) with p-cresol is in accordance with their respective pKas except for Tet-02, which, in principle, should be the most reactive. Similar to the imidazolium electrophiles tested herein, and without being bound to any one theory, reduced reactivity of sulfonyl-tetrazoles was attributed to rapid decomposition upon exposure to aqueous solvent. Arylsulfonyl imidazolium triflates appear to react readily with all nucleophiles tested by HPLC, which can be indicative of potential stability issues in aqueous solvent. In stark contrast, arylsulfonate imidazoles show minimal activity against amino acid mimetics by HPLC and negligible labeling in the proteome as determined by ABPP. Arylsulfonyl imidazoles show balanced reactivity with nucleophiles that can be tuned by substitutions at the 4-position of the imidazole LG. Akin to sulfonyl-triazoles (see Brulet et al., 2020), a correlation was observed between probe reactivity and the EWG character of functional group modifications to the azole LG. See Figure 2E. Tuning the LG on Imyl probes provided an opportunity to explore binding specificity in cell proteomes. Probe labeling experiments in DM93 cells revealed that Imyl-01 and -TFM provided broad proteomic coverage with preferential modifications on K and Y, respectively. See Figure 4E. Despite activity against p-cresol in solution, Imyl-02 and -04 were not significantly effective probes in biological systems, which could be due to stability and / or solubility issues. In contrast, Imyl-Br showed binding activity against sites captured by Imyl- 01 and -TFM but with reduced reactivity to highlight the tunable nature of the Imyl scaffold for developing protein-targeted agents. Importantly, the unusually high preference of Imyl- TFM for tyrosine binding highlights future opportunities to further improve chemoselectivity through imidazole modifications. Ligand compounds were developed using the Imyl scaffold to ligand a restricted set of protein sites detected in Colo 205 proteomes. See Figures 5A-5C. These findings contrasted Attorney Docket No.: 3062 / 203 PCT with HPLC studies that showed larger differences in reactivity and could reflect effects from protein recognition captured by LC-MS / MS chemical proteomics. Although these findings would suggest Imyl compounds function as highly attenuated electrophiles, it was demonstrated that substitution of a more reactive triazole with an imidazole LG on an optimized PTGR2 inhibitor scaffold retained inhibitory activity and reduced off-target activity. See Figures 6A-6D. Instead, it is proposed that sulfonyl-imidazoles, akin to aryl fluorosulfates (Mortenson et al., 2018), are well positioned for appending to high affinity binding elements to develop targeted covalent inhibitors with enhanced stability and selectivity. In conclusion, a suite of SufAz probes was synthesized to explore the ability of various nitrogen-containing 5-membered azoles to undergo covalent reaction with amino acid residues in the proteome. Sulfonyl-imidazoles were identified as tunable electrophiles with tempered reactivity in the proteome compared to established SuTEx compounds (Brulet et al., 2020). The ability for reactivity tuning combined with moderate proteome-wide coverage of tyrosine and lysine sites positions sulfonyl-imidazoles as a tempered electrophile for covalent targeting of functional protein sites. REFERENCES All references listed in the instant disclosure, including but not limited to all patents, patent applications and publications thereof, scientific journal articles, and database entries (including but not limited to UniProt, EMBL, and GENBANK® biosequence database entries and including all annotations available therein) are incorporated herein by reference in their entireties to the extent that they supplement, explain, provide a background for, and / or teach methodology, techniques, and / or compositions employed herein. The discussion of the references is intended merely to summarize the assertions made by their authors. No admission is made that any reference (or a portion of any reference) is relevant prior art. Applicants reserve the right to challenge the accuracy and pertinence of any cited reference. Agback & Agback (2018) Sci Rep 8:10078. Albaneze-Walker et al. (2009) iOrg Lett 2009, 11, 1463-1466. Alghamdiet et al. (2021) Drug Des Devel Ther 15:3289-3312. Ausubel et al. (2003) Current Protocols in Molecular Biology, John Wylie & Sons, Inc, New York, New York, United States of America. Anderson & Whiting (2003) J Org Chem 68:6160-6163. Bolding et al. (2022) Angew Chem Int Ed Engl 61:e202204565. Brulet et al. (2020) J Am Chem Soc 142:8270-8280. Attorney Docket No.: 3062 / 203 PCT Ciancone et al. (2023) J Am Chem Soc 145:11056-11066. Cívicos et al. (2011) Chem Lett 40:907-909. Cívicos et al. (2012) Adv Synth Catal 354:2771-2776. Cívicos et al. (2013) Adv Synth Catal 355:203-208. Cruite et al. (2023) ACS Med Chem Lett 14:1576-1581. Efimova et al. (2009) Russ J Org Chem 45:725-727. Fevig et al. (1988) Steroids 51471-497. Fox (1943) Chem Rev 32:47-71. Fujishima et al. (2012) J Am Chem Soc 134:3961-3964. Gait (1984) Oligonucleotide Synthesis: A Practical Approach, IRL Press, Oxford, England. Gennaro (ed.) (1985) Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania, United States of America. Gennaro (ed.) (1990) Remington’s Pharmaceutical Sciences, 18th ed., Mack Pub. Co., Easton, Pennsylvania, United States of America, Gennaro (ed.) (2003) Remington: The Science and Practice of Pharmacy, 20th edition., Lippincott, Williams & Wilkins, Philadelphia, Pennsylvania, United States of America.Goddard-Borger & Stick (2007) Org Lett 9:3797-3800. Glover (1985) DNA Cloning: A Practical Approach. Oxford Press, Oxford, England. Haas et al. (2008) Physiol Rev 88:1183-1241. Harlow & Lane (1988) Antibodies: A Laboratory Manual, Cold Spring Harbor Publications, Cold Spring Harbor, New York, United States of America. Holm et al. (2000) Annu Rev Nutr 20:365-393. Huang et al. (2019) ACS Chem Biol 14:192-197. Huang et al. (2021) Chem Commun (Camb) 57:9578-9581. Keith (2008) J Org Chem 73:327-330. Kovacs et al. (2012) Org Lett 14:2022-2025. Kwon et al. (2020) Org Lett 22:5511-5516. Lee et al. (2020) J Am Chem Soc 142:14993-15003. Long & Cravatt (2011) Chem Rev 111:6022-6063. Massa et al. (1992) Eur J Med Chem 27:495-502. Matsuo et al. (2013) Chem Sci 4:2573-2580. Mertins et al. (2018) Nat Protoc 13:1632-1661. Monjoint & Ruasse (1984) Tetrahedron Lett 25:3183-3186. Attorney Docket No.: 3062 / 203 PCT Moro et al. (2020)Nutrients 12:1414. Mortenson et al. (2018) J Am Chem Soc 140:200-210. O’Connell & Rapoport (2002) J Org Chem 57:4775-4777. PCT International Patent Application Publication No.2020 / 214336. Pearson et al. (2002) Org Lett 4:3099-3102. Polgar (2005) Cell Mol Life Sci 62:2161-2172. Potter et al. (2016) J Org Chem 81:3443-3446. Rauniyar & Yates, 3rd (2014) J Proteome Res 13:5293-5309. Reyes-Rangel et al. (2016) Tetrahedron 72:379-391. Robinson et al. (1998) Tetrahedron 54:981-996. Roe et al. (1996) DNA Isolation and Sequencing: Essential Techniques, John Wiley, New York, New York, United States of America. Ross & Crow (2007) J Biochem Mol Toxicol 21:187-196. Sambrook et al. (1989) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Publications, Cold Spring Harbor, New York, United States of America. Sarvary & Maleki (2015) Mol Divers 19:189-212. Satoh & Hosokawa (1998) Annu Rev Pharmacol Toxicol 38:257-288. Satoh & Hosokawa (2006) Chem Biol Interact 162:195-211. Shirbin et al. (2010) Tetrahedron Lett 51:2971-2974. Sundberg & Martin (1974) Chem Rev 74:471-517. Tamura et al. (2018) Nat Commun 9:1870. Thangam et al. (2018) Front Immunol 9:1873. Toroitich et al. (2021) Chembiochem 22:2134-2139. U.S. Patent No.11,680,060. Verma et al. (2013) J Chem 2013:329412. Wakayama et al. (2017) Nat Commun 8:14850. Wang et al. (2018) Acta Pharm Sin B 8:699-712. Wu et al. (2021) Trends Endocrinol Metab 32:48-61. Yamaura et al. (2016) Nat Chem Biol 12:822-830. Zhang et al. (2014) Med Res Rev 34:340-437. Zhang et al. (2022) Molecules 27:4377. It will be understood that various details of the presently disclosed subject matter can be changed without departing from the scope of the presently disclosed subject matter. Attorney Docket No.: 3062 / 203 PCT Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation.

Claims

Attorney Docket No.: 3062 / 203 PCT CLAIMS What is claimed is:

1. A compound having a structure of Formula (I) or Formula (I’):wherein: G2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, perhaloalkyl, aralkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; G3 is Oˉ or alkyl, optionally methyl; G4 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocycle, aralkyl, substituted aralkyl, substituted aryloxy, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; and Aˉ is present or absent, wherein when G3is alkyl, Aˉ is present and is an anionic group, optionally trifluoromethanesulfonate anion (OTf), and where G3is Oˉ, Aˉ is absent.

2. The compound of claim 1, where G4 is substituted phenyl, optionally wherein G4 is phenyl substituted with alkoxy or a group having the structure -C(=O)-R, optionally wherein R is amino, alkylamino, dialkylamino, or an optionally substituted nitrogen- containing heterocycle.

3. The compound of claim 1 or claim 2, where G2is selected from halo, trifluoromethyl, aryl, and heteroaryl, optionally pyridyl.

4. The compound of claim 3, where G2 is selected from 2-pyridyl and 3-pyridyl.

5. The compound of any one of claims 1-4, wherein the compound of Formula (I) has a structure of Formula (IIa) or (IIb):Attorney Docket No.: 3062 / 203 PCTwherein: G2is as defined for Formula (I); and R1 is selected from aryl, heteroaryl, substituted aryl, or substituted heteroaryl, optionally substituted phenyl; or a pharmaceutically acceptable salt thereof.

6. The compound of claim 5, wherein R1 is alkoxy-substituted phenyl, optionally methoxy-substituted phenyl.

7. The compound of claim 6, wherein R1is 2-methoxyphenyl.

8. The compound of claim 1, wherein the compound is selected from KY-2, KY-5, KY- 342, KY-6, Imyl-01+, Imate-01; RJG-3017, and RJG-3016.

9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of any one of claims 1-8 or a pharmaceutically acceptable salt thereof.

10. A compound selected from RJG-2096, Tet-02, Tet-03, and Tet-04.

11. A method of covalently modifying a peptide or protein, the method comprising: providing a sample comprising a peptide or protein; and contacting the sample with a compound of any one or claims 1-8 or a pharmaceutical composition of claim 9, thereby providing a covalently modified peptide or protein, optionally wherein the covalently modified peptide or protein comprises a covalently modified tyrosine or lysine residue.

12. The method of claim 11, wherein the peptide or protein is selected from a glutathione- S-transferase enzyme, optionally glutathione-S-transferase Pi (GSTP1); prostaglandin reductase 2 (PTGR2); aldo-keto reductase family member C1 (AKR1C1); and aldehyde dehydrogenase 3 family member A1 (ALDH3A1).Attorney Docket No.: 3062 / 203 PCT 13. A method of inhibiting prostaglandin reductase 2 (PTGR2), wherein the method comprises contacting a sample comprising PTGR2 the with an effective amount of a compound of any one of claims 1-8 or a pharmaceutical composition of claim 9.

14. The method of claim 13, wherein the sample comprising PTGR2 is a biological sample selected from a biological fluid, a cell culture, a cell extract, a tissue, a tissue extract, an organ, or an organism.

15. The method of claim 13 or 14, wherein the compound has a 50% inhibitory concentration (IC50) for PTGR2 of about 25 micromolar or less and / or has reduced off- target effects compared to contacting the sample with a sulfonyl-triazole compound, optionally RJG-2096.

16. The method of any one of claims 13-15, wherein the compound is a compound of Formula (IIb):, wherein: G2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, perhaloalkyl, aralkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; and R1 is selected from aryl, heteroaryl, substituted aryl, or substituted heteroaryl, optionally substituted phenyl; or a pharmaceutically acceptable salt thereof.

17. The method of claim 16, wherein R1 is alkoxy-substituted phenyl, optionally methoxy- substituted phenyl.

18. The method of claim 17, wherein R1is 2-methoxyphenyl.

19. The method of claim 13, wherein the compound is RJG-3017 or RJG-3016.

20. The method of any one of claims 13-19, wherein the contacting provides a covalently modified PTGR2, optionally wherein the covalently modified PTGR2 is covalently modified at tyrosine 100 (Y100).

21. A method of inhibiting a glutathione-S-transferase enzyme (GST), optionally glutathione-S-transferase Pi (GSTP1), wherein the method comprises contacting aAttorney Docket No.: 3062 / 203 PCT sample comprising the GST with an effective amount of a compound of any one of claims 1-8 or a pharmaceutical composition of claim 9.

22. The method of claim 21, wherein the sample comprising the GST is a biological sample selected from a biological fluid, a cell culture, a cell extract, a tissue, a tissue extract, an organ, or an organism.

23. The method of claim 21 or 22, wherein the compound has a 50% inhibitory concentration (IC50) for GSTP1 of about 5000 nanomolar or less and / or has reduced off-target effects compared to contacting the sample with a sulfonyl-triazole compound, optionally RJG-2096.

24. The method of any one of claims 21-23, wherein the compound is a compound of Formula (IIb):, wherein: G2is selected from the group consisting of H, halo, alkyl, substituted alkyl, perhaloalkyl, aralkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; and R1is selected from aryl, heteroaryl, substituted aryl, or substituted heteroaryl, optionally substituted phenyl; or a pharmaceutically acceptable salt thereof.

25. The method of claim 24, wherein R1is alkoxy-substituted phenyl, optionally methoxy- substituted phenyl.

26. The method of claim 25, wherein R1 is 2-methoxyphenyl.

27. The method of claim 26, wherein the compound is RJG-3017 or RJG-3016.

28. The method of any one of claims 21-27, wherein the contacting provides a covalently modified GST, optionally wherein the covalently modified GST comprises a covalently modified tyrosine.

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