14 results about "Binding selectivity" patented technology

The invention relates to the technical field of biological pharmacy, in particular to an application of N-[(3-chlorphenyl) methyl]-5-methyl-4-[(morpholine-4-yl) methyl]-1, 2-azole-3-formamide in preparation of an anti-melanoma drug and a preparation method of the N-[(3-chlorphenyl) methyl]-5-methyl-4-[(morpholine-4-yl) methyl]-1, 2-azole-3-formamide. According to the invention, specific pharmacophore and hydrophobic / hydrophilic modification are introduced in structure, so that the combination selectivity and stability of the compound and a target spot are improved; on the action mechanism, the compound can effectively interfere with a Bcl-3 signal channel. In-vivo experiments prove that the compound disclosed by the invention has a good tumor inhibition effect in an animal model, meanwhile, no obvious systemic toxicity is observed, and a relatively high therapeutic index is shown. In addition, the compound has good physicochemical properties and synthesis process feasibility, is convenient for industrial production, and is expected to become a novel candidate drug for clinical melanoma resistance.

Provided herein are methods for discovering and optimizing lasso peptides using an integrated and iterative workflow involving structure-based design principles, in silico modeling, epitope grafting, virtual screening, genetic engineering, peptide evolution, and experimental testing. Also provided herein are lasso peptides that have been discovered and optimized for binding selectivity, binding affinity, biological activity, and other properties using the methods described herein.

Provided is a compound that has high binding selectivity with respect to α-synuclein aggregates.Provided is a compound represented by the following formula (I), (II), or (III), a pharmaceutically acceptable salt thereof, or a solvate thereof.

The invention belongs to the technical field of hydrogel, and particularly relates to acylhydrazone bond system hydrogel and a preparation method and application thereof.The system is composed of two kinds of modified gel, one kind of modified gel is amino-containing modified sodium hyaluronate (NorHA-ADH), the other kind of modified gel is aldehyde-containing oxidized sodium alginate (OSA), and after the two kinds of components are mixed, the hydrogel is prepared into a hydrogel solution through a sol-gel method. A controllable double-crosslinking network can be formed through crosslinking of an acylhydrazone bond, and the drug carrier has various technical advantages which are mainly reflected in (1) a specific drug carrying mechanism: molecular binding selectivity is remarkably improved through directional covalent binding of an aldehyde group component and a drug amino group; (2) gradient release regulation and control: utilizing the controllable hydrolysis characteristic of an acylhydrazone bond in an acid environment to realize dynamic matching between the drug release rate and the pH value of a focus microenvironment; and (3) structure programmability: by adjusting the ratio of functional groups of the precursor, the mechanical strength and degradation kinetics of the hydrogel can be systematically adjusted to adapt to the requirements of different treatment scenes, and the controlled release effect of the system on amino drugs and the treatment effect on related diseases are obviously superior to those of a traditional sodium alginate system.

The application discloses a phthalocyanine-based photo-PROTAC drug and a preparation method and application thereof, and mainly adopts a chemical synthesis method of amino and carboxyl coupling, takes photosensitizer ZnPc and BRD4 ligand JQ1 (a BRD4 inhibitor) as a structural main body, selects a polyethylene glycol (PEG) chain with different lengths as a linker of ZnPc and JQ1, and constructs a photo-PROTAC drug with BRD4 as a target point. The raw material of the application has a wide source, and the preparation method is simple. The drug utilizes the expression of BRD4 in bladder cancer tumor tissues, and realizes efficient degradation of PROTAC independent of E3 ubiquitinase by combining selective tumor site light. Meanwhile, BRD4 degradation destroys the antioxidant and hypoxic inhibition barrier of PDT, and realizes synergistic effect of PDT and PROTAC.

The invention provides a fluorescent dye and a preparation method and application thereof, the fluorescent dye has the following chemical structural formula: wherein R1 and R2 are respectively and independently selected from H, Cl, Br and I; r3 is selected from alkyl, and n is a positive integer. The problems that a traditional dye is low in binding selectivity and overlapped in life fingerprints in a complex lipid system are solved, and high-resolution recognition of lipid types such as CE, TG and PL in a serum environment is achieved. Meanwhile, extraction-free in-situ classification detection can be carried out on the lipid, when the fluorescent dye is used for the probe, dependence of chromatography and mass spectrometry technologies on tedious pretreatment can be broken through based on the synergistic effect of the fluorescent probe and the fluorescence lifetime imaging technology, and serum lipid spatial distribution analysis and relative quantification of components are achieved. In addition, a standardized classification criterion can be established, and a quantifiable lipid subtype analysis tool is provided for clinic.

Provided is an Fc variant which has improved half-life by binding to and unbinding from FcRn in a pH-dependent manner, and which has improved selective binding to Fcγ receptors. Compared to a wild-type human antibody Fc domain and conventional antibodies approved as antibody therapeutic agents, the present human antibody Fc domain variants have a lower capacity to bind to immune-inhibiting receptors FcγRIIb and FcγRIIIb and have a higher capacity to bind to immune-activating receptor FcγRIIa (increased A / I ratio), thereby having a remarkably improved effector function and having maximized half-life in blood in which excellent pH-selective FcRn binding and unbinding capacity is exhibited, and thus bind to numerous peptide drug therapeutics having short half-life and retention time in the body so that long-term drug efficacy through increased blood half-life can be exhibited, and can maximize the immune mechanism of therapeutic protein drugs.

This invention discloses a benzo[selenazole] derivative, its preparation method, and its application in the preparation of RNA fluorescent probes. The benzo[selenazole] derivative provided by this invention has the following structural formula: [structural formula would be inserted here]. This benzo[selenazole] derivative is a typical fluorescently activated probe, exhibiting excellent selective recognition and binding ability for RNA molecules. It demonstrates excellent resistance to biological background interference and exhibits high binding selectivity and recognition specificity for RNA in both live and fixed cell systems. It possesses advantages such as high signal-to-noise ratio and excellent fluorescence photostability, making it suitable for real-time, dynamic fluorescence imaging detection of intracellular RNA. It can achieve in-situ visualization and tracing of changes in subcellular RNA distribution and content. The synthesis method of the benzo[selenazole] derivative provided by this invention has a clear process flow, mild and stable reaction conditions, requires no demanding equipment or special reagents, and uses commercially available and readily available conventional chemicals as raw materials. The operation is simple and easy to perform, with strong overall process operability, making it suitable for large-scale production applications.

Provides an α-synuclein aggregate binder with high binding selectivity to α-synuclein aggregates. An α-synuclein aggregate binder comprising: a compound of formula (I), a pharmaceutically permissible salt thereof, or a solvate thereof (in formula (I), R1 and R2 are each independently selected from hydrogen, alkyl, alkenyl, acyl, and hydroxyalkyl; R3 is hydrogen or halogen; ring A is a benzene ring or a pyridine ring; ring B is of formula (i) or (ii); and R4 and R5 are each independently selected from hydrogen, hydroxyl, alkoxy, haloalkoxy, halohydroxyalkoxy, and aminoalkyl).

The present invention provides an α-synuclein aggregate binding agent that has high binding selectivity for an α-synuclein aggregate.The α-synuclein aggregate binding agent contains a compound represented by a formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof:in the formula (I), R1 and R2 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, acyl, and hydroxyalkyl; R3 is hydrogen or halogen; the ring A is a benzene or pyridine ring; the ring B is represented by the following formula (i) or (ii):R4 and R5 are each independently selected from the group consisting of hydrogen, hydroxy, alkoxy, haloalkoxy, halohydroxyalkoxy, and aminoalkyl.

The present invention relates to Fc variants which have improved half-life by binding to and unbinding from FcRn in a pH-dependent manner and which have improved selective binding to Fcyreceptors. Novel human Fc domain variants of the present invention have lower capacity to bind to immune inhibiting receptor FcyRIIb and have higher capacity to bind to immune activating receptor FcyRIIa (increased A / I ratio) than a wild-type human antibody Fc domain and conventional antibodies approved as antibody therapeutic agents, thereby having remarkably improved ADCP induction ability and having maximized half-life in blood in which excellent pH-selective FcRn binding and unbinding capacity is exhibited, and thus bind to numerous peptide drug therapeutics having a low half-life and retention time in the body so as to enable the peptide drug therapeutics to have an increased blood half-life and exhibit long-term drug efficacy, and can maximize the immune mechanism of therapeutic protein drugs so as to be effectively used as an improved antibody drug.

Provided are Fc variants having improved half-life by binding to and unbinding from FcRn in a pH-dependent manner and which have improved selective binding to Fcγ receptors. The human Fc domain variants have lower capacity to bind to immune inhibiting receptor FcγRIIb and have higher capacity to bind to immune activating receptor FcγRIIa (increased A / I ratio) than a wild-type human antibody Fc domain and conventional antibodies approved as antibody therapeutic agents, thereby having remarkably improved ADCP induction ability and having maximized half-life in blood in which excellent pH-selective FcRn binding and unbinding capacity is exhibited, and thus bind to numerous peptide drug therapeutics having a low half-life and retention time in the body to enable the peptide drug therapeutics to have an increased blood half-life and exhibit long-term drug efficacy, and can maximize the immune mechanism of therapeutic protein drugs to be effectively used as an improved antibody drug.

The invention relates to a PEGylated CD16a antibody and application thereof. A Fab region and an Fc region of the PEGylated CD16a antibody are mutated; the mutation of the Fc region comprises any one of L234A, L235A, M252Y, S254T, T256E or K447C or a combination of at least two of the L234A, the L235A, the M252Y, the S254T, the T256E and the K447C; the K447C site of the Fc region of the PEGylated CD16a antibody is connected with polyethylene glycol. The Fab region and the Fc region are mutated, interaction with CD16a is enhanced through charge complementation, inhibitory receptor combination is reduced, the NK cells are selectively activated, and combination with FcRn is enhanced, so that amplification of the NK cells is improved. By increasing the molecular size, the kidney clearance is reduced, the antibody is protected from being degraded by protease, and the half-life period is prolonged.

The application provides a fluorescent dye and a preparation method and application thereof, and the fluorescent dye has the following chemical structural formula: wherein R1 and R2 are independently selected from H, Cl, Br and I; R3 is selected from alkyl,, and wherein n is a positive integer. The problems of low binding selectivity and overlapping of life fingerprints of traditional dyes in a complex lipid system are solved, and high-resolution identification of lipids such as CE, TG and PL in a serum environment is realized. Meanwhile, the lipids can be classified and detected in situ without extraction, and when the fluorescent dye is used as a probe, the dependence on chromatography and mass spectrometry technology for complicated pretreatment can be broken based on the synergistic effect of the fluorescent probe and the fluorescent lifetime imaging technology, so that the spatial distribution analysis and relative quantification of serum lipids are realized. In addition, a standardized classification criterion can be established, and a quantifiable lipid subtype analysis tool is provided for clinical use.