27 results about "Peptide mimetic" patented technology

The invention provides a method and a system for screening and constructing a small molecule polypeptide simulant based on interaction between proteins, relates to the technical field of biology, and comprises the following steps: predicting an interaction model of RECK protein and ADAM10 protein through a molecular docking platform, and analyzing interaction sites of the RECK protein and the ADAM10 protein. And then, determining a KAZAL region of the RECK protein according to the interaction site, and predicting a sequence structure of the KAZAL region. And then carrying out molecular docking on the KAZAL region and ADAM10 protein, designing a plurality of peptide fragments with the length of 30 amino acids, and screening the peptide fragment sequence with the highest score as candidate polypeptide. And finally, performing species homology comparison and quality control detection on the candidate polypeptide, and verifying the binding capacity and biological function of the candidate polypeptide to ADAM10 protein through cell experiments. The invention provides a method for screening to obtain a polypeptide simulant specifically bound with ADAM10 protein. The polypeptide simulant can be used for treating ADAM10 related diseases.

The present invention provides synthetic peptide compounds and uses thereof for therapy and diagnostics of complement-mediated diseases, such as inflammatory diseases, autoimmune diseases, and microbial and bacterial infections; and non-complement-mediated diseases, such cystic fibrosis and various acute diseases. The invention is directed to modifications of a synthetic peptide of 15 amino acids from the Polar Assortant (PA) peptide, which is a scrambled peptide derived from human Astrovirus protein. In some embodiments, the invention is directed to peptide compounds that are peptide mimetics, peptide analogs and / or synthetic derivatives of PA (e.g., sarcosine derivatives) having, for example, internal peptide substitutions, and modifications, including PEGylation at the N-terminus and C-terminus. The invention further provides methods of selecting at least one synthetic peptide for treating various conditions.

The present invention provides synthetic peptide compounds and uses thereof for therapy and diagnostics of complement-mediated diseases, such as inflammatory diseases, autoimmune diseases, and microbial and bacterial infections; and non-complement-mediated diseases, such cystic fibrosis and various acute diseases. The invention is directed to modifications of a synthetic peptide of 15 amino acids from the Polar Assortant (PA) peptide, which is a scrambled peptide derived from human Astrovirus protein. In some embodiments, the invention is directed to peptide compounds that are peptide mimetics, peptide analogs and / or synthetic derivatives of PA (e.g., sarcosine derivatives) having, for example, internal peptide substitutions, and modifications, including PEGylation at the N-terminus and C-terminus. The invention further provides methods of selecting at least one synthetic peptide for treating various conditions.

The present invention provides peptide compounds that regulate the complement system and methods of using these compounds. The invention is an isolated, purified peptide of 30 amino acids derived from human astrovirus protein, called CP1. The invention is directed to peptide compounds that are peptide mimetics, peptide analogs and / or synthetic derivatives of CP1 having, for example, internal peptide deletions and substitutions, deletions and substitutions at the N-terminus and C-terminus, and that are able to regulate complement activation. The invention further provides pharmaceutical compositions of therapeutically effective amounts of the peptide compounds and a pharmaceutically acceptable carrier, diluent, or excipient for treating a disease or condition associated with complement-mediated tissue damage.

The present invention discloses a PTP1B peptide inhibitor, BimBH3-12-F12A, having the following structural formula: #imgabs0#. This peptide mimetic compound is derived from the core 12-peptide of the BimBH3 domain, in which Phe (F) at position 12 is replaced by Ala (A). It is prepared using peptide solid-phase synthesis, and all amino acids in its structure are natural amino acids. The PTP1B peptide inhibitor, BimBH3-12-F12A, has significant PTP1B inhibitory activity and has potential application in the development of drugs for PTP1B-targeted diseases such as diabetes, cancer, and Alzheimer's disease.

The present invention relates to Mitochondrial Fission Factor (MFF)-derived peptides or peptide mimetics and to methods of making MFF-derived peptides or peptide mimetics. Also provided are methods of treating a disease in a subject in need thereof, comprising administering to the subject an effective amount of a MFF-derived peptide or peptide mimetic.

EphA2 targeting agents developed herein are potent peptide-mimetics with high affinity (Kds 8-20 nanomolar) for the ligand binding domain, called targefrin. Monomeric versions of targefrin act as antagonists while dimeric versions (targefrin-dimer) of the agent cause receptor internalization and degradation via a lysosomal pathway. Hence, targefrin-dimer agents are effective in reducing pro-oncogenic EphA2 levels in cancer cells when used as single agents or in combination with standards of care. Targefrin-dimers can also sensitive cancer cells that developed resistance to EGER or BRAE inhibitors, and potentially other anti-cancer agents. In addition, the dimeric agents can be conjugated with chemotherapy such as paclitaxel to deliver selectively cytotoxic agent to EphA2 expressing cancer cells. Monomeric agents can be linked to chemotherapy via a stable cleavable linker, accumulate the cytotoxic at the tumor, that then would enter the tumor. Novel composition and examples of these applications are reported.

The invention discloses a polypeptide ligand targeting fibroblast activating protein and application of the polypeptide ligand. Part of the structure in the cyclopeptide skeleton of the ligand is a peptide mimetic skeleton structure aiming at an FAP target, the specific binding force with the FAP is stronger, the ligand has stronger FAP targeting, higher tumor specificity and faster kidney clearance rate, and the retention time at a tumor part is longer, so that the ligand has an obvious inhibiting effect on the FAP and can be used as or used for preparing an FAP inhibitor; the compound can be connected with one of a fluorophore, a radionuclide for diagnosis, a chelating group containing the radionuclide for diagnosis and the like to serve as or be used for preparing a developing agent for developing tumors, inflammatory sites, infected sites and the like. The polypeptide can be connected with one of therapeutic radionuclide, a chelating group containing the therapeutic radionuclide, a cytotoxin group, other functional groups and the like to serve as or be used for preparing targeted polypeptide coupling drugs for treating diseases such as tumors, inflammations, infection and the like; the effect is good, the safety is high and the application is wide.

The application discloses a kind of fat cationic amphiphilic peptide mimics and its preparation method and application.The application first develops a kind of cysteine-based amphiphilic cationic peptide mimic system, then, by forming peptide bond at carboxyl terminal, introduce ethylenediamine as cationic group, while introducing aromatic ring-containing hydrophobic group in thiol side chain;Among them, cationic group provides positive charge and hydrophilicity, helps to carry out electrostatic interaction with the bacterial membrane with negative charge, while hydrophobic group helps membrane insertion phospholipid bilayer;In addition, the application tunes the amphiphilic balance of cysteine-based cationic peptide mimic by modifying N-terminal with different chain length fatty acids, and finally synthesizes fat cationic amphiphilic peptide mimic.The peptide mimic has good antibacterial activity, and is not easy to induce bacteria to produce drug resistance, and can be used for preparing drugs for treating, improving and / or preventing drug-resistant bacteria and / or drug-resistant fungal infection.

Described herein are synthetic cyclic peptide mimetics comprising alternating D-amino acids and L-amino acids and amino acid derivatives, such as aza-amino acids and azasulfuryl-amino acids. Optionally, the cyclic peptide mimetics may be conjugated to another agent via a linker to form cyclic peptide mimetic conjugates. The cyclic peptide mimetics described herein may be used as diagnostic or therapeutic agents for diagnosis or treatment of amyloidogenic diseases.

The present invention discloses a PTP1B peptide inhibitor, BimBH3-12-G9A, having the following structural formula: #imgabs0#. This peptide mimetic compound is derived from the core 12-peptide of the BimBH3 domain, in which Gly (G) at position 9 is replaced by Ala (A). It is prepared using peptide solid-phase synthesis, and all amino acids in its structure are natural amino acids. The PTP1B peptide inhibitor, BimBH3-12-G9A, has significant PTP1B inhibitory activity and has potential application in the development of drugs for PTP1B-targeted diseases such as diabetes, cancer, and Alzheimer's disease.

The invention discloses a peptide simulant and a preparation method thereof, 3-oxetanone and 3-methyl-1-nitrobutane are used as raw materials, and all reactions are carried out to obtain a target product. The peptide simulant is novel in structure and has potential biological activity, adopted protecting groups and functional groups are good in compatibility, and follow-up structural modification is facilitated; the designed synthesis route is simple, the reaction condition is mild, and amplification is easy; the yield of each step is high, and the product is easy to purify.

The present invention relates to mimics of post-translationally modified naturally occurring peptides, wherein said peptide mimics bind to a peptide-binding groove of human leukocyte antigen (HLA) molecules to the same extent as the naturally occurring post-translationally modified peptide, wherein said peptide mimics are recognized by T cells to the same extent as the naturally occurring post-translationally modified peptide, and additionally wherein said peptide mimics have a three-dimensional structure substantially identical to said post-translationally modified naturally occurring peptide. Such peptide mimics can be used alone of bound to a carrier, and have utility inter alia in methods for the treatment, alleviation and prevention of autoimmune diseases, and as components in tolerogenic vaccines.

The present invention provides peptide compounds that regulate the complement system and methods of using these compounds. The invention is an isolated, purified peptide of 30 amino acids derived from human astrovirus protein, called CP1. The invention is directed to peptide compounds that are peptide mimetics, peptide analogs and / or synthetic derivatives of CP1 having, for example, internal peptide deletions and substitutions, deletions and substitutions at the N-terminus and C-terminus, and that are able to regulate complement activation. The invention further provides pharmaceutical compositions of therapeutically effective amounts of the peptide compounds and a pharmaceutically acceptable carrier, diluent, or excipient for treating a disease or condition associated with complement-mediated tissue damage.

The present invention discloses a PTP1B peptide inhibitor, BimBH3-12-I8A, having the following structural formula: #imgabs0#. This peptide mimetic compound is derived from the core 12-peptide of the BimBH3 domain, in which Ile (I) at position 8 is replaced by Ala (A). It is prepared using a peptide solid-phase synthesis method, and all amino acids in its structure are natural amino acids. The PTP1B peptide inhibitor, BimBH3-12-I8A, has significant PTP1B inhibitory activity and has potential application in the development of drugs for PTP1B-targeted diseases such as diabetes, cancer, and Alzheimer's disease.

The invention relates to chemical compounds useful as structural mimetics of peptides comprising polyproline helix structures, preferably polyproline-type II (PPII) helix structures. The invention further relates to the medical use of the chemical compounds in the treatment of a medical condition associated with a modified intracellular signal transduction process mediated by a poly-proline helix structure and a protein having a binding domain binding to said polyproline helix structure such as an infectious disease, immune disease, neurological disease, cardiometabolic disease and a cancerous disease. The invention further relates to pharmaceutical compositions comprising a compound of the present invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The invention further relates to an in vitro method for modifying an intracellular signal transduction process mediated by a poly-proline helix structure, comprising contacting a compound of the invention with a biological cell.

The present invention relates to an injectable delivery system for long-acting administration of drugs. The present invention includes compounds formed at least in part from peptidomimetic molecules. The compound is configured to link one or more drug molecules, and is further configured to release the one or more drug molecules under physiological conditions. A solution of the compound forms a hydrogel in response to an endogenous enzyme of a human or animal. A solution of the compound can be applied to the skin where it forms a hydrogel upon application, and any drug attached to the compound will then be gradually released.

The present invention belongs to the field of organic chemistry, and specifically relates to a preparation method and application of a hydantoin dimer and its derivatives. The present invention obtains a series of hydantoin dimer derivatives through a simple and easy liquid phase synthesis. The synthesis and structural optimization of such small molecule antimicrobial peptide mimetics are relatively easy to improve activity, and the hydantoin dimer compounds have good stability and are not affected by protease degradation. The present invention measured the antimicrobial activity and mechanism of action of the successfully synthesized hydantoin dimer compounds. The results showed that the bactericidal efficiency and stability of the dimer were greatly improved, and the bacterial strain could be quickly killed within 1 hour. The mechanism of action is the same as that of previous work, which is to directly interact with the bacterial cell membrane to damage it, thereby causing bacterial cell death.

This disclosure provides engineered polypeptides with Atg8 binding activity. The polypeptides comprise a LC-3 interacting motif comprising one or more mutations relative to a wild type LC3 -interacting motif. Also provided are heterobifunctional compounds, compositions comprising the compounds or engineered polypeptides, and methods of using the compounds or engineered polypeptides.

The present invention discloses a PTP1B peptide inhibitor, BimBH3-12-R7A, having the following structural formula: #imgabs0#. This peptide mimetic compound is derived from the core 12-peptide of the BimBH3 domain, in which Arg (R) at position 7 is replaced by Ala (A). It is prepared using peptide solid-phase synthesis, and all amino acids in its structure are natural amino acids. The PTP1B peptide inhibitor, BimBH3-12-R7A, has significant PTP1B inhibitory activity and has potential application in the development of drugs for PTP1B-targeted diseases such as diabetes, cancer, and Alzheimer's disease.

Described herein is a peptide comprising an amino acid sequence having two or more GXX repetitive sequences wherein each X is independently proline (Pro) or hydroxyproline (Hyp). The invention also relates to salt forms and peptidomimetics derived from such peptides.

The invention discloses a tumor marker based on P5CS RNA binding activity and application thereof, and belongs to the technical field of biomedicine. Wherein P5CS is low in expression in gastric cancer and renal clear cell carcinoma, and the potential of P5CS as a tumor detection biomarker is revealed; the invention proposes that the P5CS regulates the growth of tumor cells in an enzyme activity independent manner for the first time, and proves that the deletion of the P5CS RNA binding domain (RNA binding domain, RBD) can significantly inhibit the tumor inhibition function, and P5CS inhibits protein translation and finally inhibits tumor progression by binding RNA, so that P5CS RNA binding domain peptide simulation drugs or activators can be developed, the expression of tumor-associated proteins can be specifically regulated and controlled, and the application of the P5CS RNA binding domain peptide simulation drugs or activators is developed. The cancer inhibition function of P5CS is enhanced, and the tumor treatment effect is optimized.

The invention provides an indole antibacterial peptide simulant with antibacterial activity and a preparation method and application thereof, and relates to the technical field of medicinal chemistry, the chemical structural formula of the indole antibacterial peptide simulant is shown as the following (I), and n and R in the formula are defined as the specification; in-vitro antibacterial activity experiments prove that the indole antibacterial peptide simulant disclosed by the invention has relatively good antibacterial activity on gram-positive bacteria such as staphylococcus aureus, bacillus subtilis and enterococcus faecalis, and has the characteristics of low cytotoxicity, low hemolysis and difficulty in generating drug resistance; the compound can be applied to preparation of drugs for resisting bacteria or treating bacterial infection. (I)

The present invention discloses a PTP1B peptide inhibitor, BimBH3-12-Q3A, having the following structural formula: #imgabs0#. This peptide mimetic compound is derived from the core 12-peptide of the BimBH3 domain, in which Gln (Q) at position 3 is replaced by Ala (A). It is prepared using peptide solid-phase synthesis, and all amino acids in its structure are natural amino acids. The PTP1B peptide inhibitor, BimBH3-12-Q3A, has significant PTP1B inhibitory activity and has potential application in the development of drugs for PTP1B-targeted diseases such as diabetes, cancer, and Alzheimer's disease.

The invention relates to a self-assembly oligopeptide mimic enzyme, a polypeptide-metal ion composite mimic enzyme and application thereof.The self-assembly oligopeptide mimic enzyme prepared through the method takes self-assembly polypeptide as a raw material, a nanobelt microstructure with the regular width is formed through self-assembly, and compared with the common protein disordered aggregation and amyloid protein fiber morphology in natural enzymes, the nanoribbon microstructure has the advantages that the structure is simple, and the application range is wide. The catalyst has a larger active site exposure space, so that the catalyst has high catalytic activity, and shows more excellent catalytic activity on decomposition of 4-nitrophenyl acetate and L-type dopa after being coordinated with different metal ions. Stability tests show that the self-assembled oligopeptide mimic enzyme prepared by the invention has high stability of dilution, freezing, acid-base and the like, and compared with natural enzymes, the self-assembled oligopeptide mimic enzyme is more suitable for catalytic reaction in more complex and harsh reaction environments.

Disclosed in the present invention are a small-molecule antibacterial peptide mimetic and the use thereof. The small-molecule antibacterial peptide mimetic is obtained by means of chemical modification at the amino terminus, the carboxyl terminus or on a side-chain sulfydryl group on the basis of a cysteine skeleton structure, and has general formula (I). The small-molecule antibacterial peptide mimetic can cause cell membrane depolarization, destroy cell membrane integrity, rapidly kill bacteria and inhibit biofilm formation, has certain biofilm clearance activity, and is less likely to induce bacterial drug resistance. The small-molecule antibacterial peptide mimetic has good activity against Gram-positive bacteria, shows good antibacterial activity against drug-resistant bacteria such as MRSA and VRE, and therefore can solve the problem of the current shortage of drugs against drug-resistant bacteria, has the potential to replace or assist currently used clinical antibiotics in treating infectious diseases caused by various drug-resistant bacteria, and can be used for the treatment of infectious diseases caused by both sensitive bacteria and drug-resistant bacteria, The small-molecule antibacterial peptide mimetic has efficient antibacterial activity and low toxicity, and is not influenced by traditional drug-resistant mechanisms.

The invention belongs to the technical field of antibacterial peptides, and provides an antibacterial peptide simulant based on a cinnamic acid skeleton as well as a preparation method and application of the antibacterial peptide simulant. The antibacterial peptide simulant based on the cinnamic acid skeleton comprises an ammonium salt antibacterial peptide simulant and / or a guanidine salt antibacterial peptide simulant, and is prepared by the following steps: taking 4-bromomethyl biphenyl as a raw material, and performing bromination reaction to obtain an intermediate 1; then the intermediate 1 and (2E)-3-phenyl-2-acrylic acid are subjected to an amide condensation reaction and a Boc removal protection reaction to obtain an ammonium salt antibacterial peptide simulant, and then the guanidinium antibacterial peptide simulant is obtained through a guanidinylation reaction and a Boc removal protection reaction. The antibacterial peptide simulant based on the cinnamic acid skeleton has excellent antibacterial activity, and also has the characteristics of strong stability, low toxicity, simple structure, rapid sterilization and difficult generation of drug resistance, and the clinical application of the antibacterial peptide simulant is greatly promoted.