# US 7,745,144 B2 · Peptides and their utility in modulation of behavior of cells expressing α3β1 integrins > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,745,144 B2 - Document ID: US7745144B2 - Status: Granted - Kind: B2 - Application number: 11/466,718 - Filed: 2006-08-23 - Published: 2008-10-09 - Granted: 2010-06-29 - Earliest claimed: 1999-07-15 - Assignees: The United States of America as represented by the Department of Health and Human Services - Inventors: David D. Roberts; Henry C. Krutzsch - Web page: https://patentgrep.com/patent/US7745144B2 ## CPC - C07K 7/06: having 5 to 11 amino acids - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 27/02: Ophthalmic agents - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 35/00: Antineoplastic agents - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract The present invention relates to a peptide comprising the sequence R1—X1—X2—X3—X4—R2, wherein X1 is selected from the group consisting of N, Q, D and S; X2 is selected from the group consisting of V, I and L; X1 is selected from the group consisting of R and K; and X4 is selected from the group consisting of V, I, L and F; R1 is a hydrogen or a peptide of 1 to 6 amino acids, and acyl or an aryl group; and R2 is a peptide of 1 to 3 amino acids, a hydroxide or an amide. The invention also relates to partial or full retro-inverso peptides comprising the above sequences. The invention also relates to peptide-substrate combination comprising a substrate suitable for cell growth and the peptide of the invention, and to a vascular graft and an artificial blood vessel comprising the peptide-substrate combination. The invention also relates to a pharmaceutical composition and a peptide conjugate comprising the peptide of the invention. The invention also relates to a method of inhibiting adhesion of a cell expressing α3β1 integrin to an extracellular matrix, inhibiting α3β1-integrin-mediated cell motility, inhibiting α3β1-integrin mediated cell proliferation, promoting α3β1-integrin mediated cell proliferation and inhibiting angiogenesis utilizing the peptides of the invention. ## Claims ### Claim 1 A peptide comprising the sequence R1—X1—X2—X3—X4—R2— or full retro-inverso sequences thereof, wherein X1 is selected from the group consisting of N, Q, D and S; X2 is V; X3 is R; and X4 is selected from the group consisting of L and F; R1 is a peptide comprising the sequence selected from FQGVLQ (SEQ ID NO:13), FAGVLQ (SEQ ID NO:14), FQGVAQ (SEQ ID NO:15), FQGVLA (SEQ ID NO:16), and FQGVLN (SEQ ID NO:17); and R2 is from 1 to 3 amino acids, a hydroxide or an amide, wherein the peptide is up to 12 amino acids in length and binds to α3β1 integrin, and provided that the peptide does not comprise the sequence FQGVLQNVRFVF (SEQ ID NO:6) or DVRF (SEQ ID NO:54). ### Claim 2 (depends on 1) The peptide of claim 1 wherein X1—X2—X3—X4 is selected from the group consisting of NVRF (SEQ ID NO:51), SVRF (SEQ ID NO:52), and QVRF (SEQ ID NO:53). ### Claim 3 (depends on 1) The peptide of claim 1 that comprises at least one D-amino acid. ### Claim 4 A retro-inverso synthetic peptide comprising the amino acid sequence, from C-terminal (left) to N-terminal (right): ri-R′1—X′1—X′2—X′3—X′4—R′2, wherein ri denotes a retro-inverso peptide sequence and all amino acids are D amino acids; X′1 is selected from the group consisting of N, Q, D and S; X′2 is selected from the group consisting of V, I and L; X′3 is selected from the group consisting of R and K; and X′4 is selected from the group consisting of V, I, L and F; R′1 is a peptide comprising the sequence selected from FQGVLQ (SEQ ID NO:13), FAGVLQ (SEQ ID NO:14), FQGVAQ (SEQ ID NO:15), FQGVLA (SEQ ID NO:16), and FQGVLN (SEQ ID NO:17); and R′2 is from 1 to 3 amino acids, an acyl or an aryl group, wherein the peptide is up to 12 amino acids in length and binds to α3β1 integrin and provided that the peptide does not comprise the sequence FQGVLQNVRFVF (SEQ ID NO:6). ### Claim 5 (depends on 1) A composition comprising a peptide according to claim 1 and a pharmaceutically acceptable carrier. ### Claim 6 (depends on 1) A composition comprising a peptide according to claim 1 in a sterile aqueous solution. ### Claim 7 (depends on 1) A method of inhibiting adhesion of a cell expressing α3β1 integrin to an extracellular matrix comprising contacting said cell with a peptide according to claim 1, wherein said contacting takes place in vitro. ### Claim 8 (depends on 7) The method of claim 7 wherein the extracellular matrix comprises TSP1 or laminins. ### Claim 9 (depends on 7) The method of claim 7 wherein said cell comprises an epithelial or an endothelial cell. ### Claim 10 (depends on 7) The method of claim 7 wherein said cell is a tumor cell. ### Claim 11 (depends on 7) The method of claim 7 wherein said cell is a breast carcinoma cell or a small cell lung carcinoma. ### Claim 12 (depends on 1) A method of inhibiting α3β1 integrin-mediated cell motility, comprising contacting a cell with a peptide according to claim 1, wherein said contacting takes place in vitro. ### Claim 13 (depends on 12) The method of claim 12 wherein the cell is an epithelial cell, an endothelial cell or a malignant cell. ### Claim 14 (depends on 1) A method of inhibiting proliferation of endothelial cells, comprising contacting said cells with a peptide according to claim 1, wherein said contacting takes place in vitro. ### Claim 15 (depends on 1) A method of inhibiting proliferation of small cell lung carcinoma cells, comprising contacting said cells with a peptide according to claim 1, wherein said contacting takes place in vitro. ### Claim 16 A peptide comprising the sequence R1—X1—X2—X3—X4—R2, or full retro-inverso sequences thereof, wherein X1 is selected from the group consisting of N, Q, D and S; X2 is selected from the group consisting of V, I and L; X3 is selected from the group consisting of R and K; and X4 is selected from the group consisting of V, I, L and F; R1 is a peptide comprising the sequence selected from FQGVLQ (SEQ ID NO:13), FAGVLQ (SEQ ID NO:14), FQGVAQ (SEQ ID NO:15), FQGVLA (SEQ ID NO:16), and FQGVLN (SEQ ID NO:17); and R2 is from 1 to 3 amino acids, a hydroxide or an amide, wherein the peptide is up to 12 amino acids in length and binds to α3β1 integrin, and provided that the peptide does not comprise the sequence FQGVLQNVRFVF (SEQ ID NO:6). ### Claim 17 (depends on 16) The peptide of claim 16, that comprises at least one D-amino acid.