STQ Peptides

Abstract

The invention describes methods for inhibiting angiogenesis in a tissue by administering an antagonist that specifically binds to a proteolyzed or denatured laminin with substantially greater affinity than to the native form of laminin. Methods utilizing such antagonists for therapeutic treatment of tumor growth, tumor metastasis or of restenosis also are described, as are methods to use such antagonists as diagnostic markers of angiogenesis in normal or diseased tissues both in vivo and ex vivo.

1 - 11 . (canceled) 
     
     
         12 . A method for inhibiting angiogenesis in a patient comprising:
 administering an angiogenesis-inhibiting effective amount of a denatured laminin selective antagonist to the patient.   
     
     
         13 . A method of detecting angiogenesis in a patient comprising:
 administering a denatured laminin selective antagonist to the patient, and detecting bound selective denatured laminin antagonist in the patient.   
     
     
         14 . A method of treating a tumor in a patient comprising:
 administering an angiogenesis-inhibiting effective amount of a denatured laminin selective antagonist to the patient.   
     
     
         15 . A method of treating metastases in a patient comprising:
 administering an angiogenesis-inhibiting effective amount of a denatured laminin selective antagonist to the patient.   
     
     
         16 . A method of treating angiogenic disease in a patient comprising:
 administering an angiogenesis-inhibiting effective amount of a denatured laminin selective antagonist to the patient.   
     
     
         17 . The method of  claim 12  wherein the denatured laminin selective antagonist is administered:
 intravenously, intraperitoneally, intramuscularly, subcutaneously, intracavity, transdermally, topically, intraocularly, orally, intranasally, or by peristaltic means.   
     
     
         18 . The method of  claim 12  wherein the denatured laminin selective antagonist dose range is 0.1 Imilligram per kilogram per day to 300 milligrams per kilogram per day. 
     
     
         19 . The method of  claim 12  wherein the denatured laminin selective antagonist dose range is 10 milligrams to 3000 milligrams. 
     
     
         20 . The method of  claim 14  wherein the denatured laminin selective antagonist is administered in combination with a chemotherapeutic agent, a radioactive material, or a cytostatic agent. 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 14  wherein the patient is a mammal. 
     
     
         24 . The method of  claim 14  wherein the patient is a human. 
     
     
         25 . A method for inhibiting tumor cell adhesion in a patient comprising:
 administering a tumor cell adhesion-inhibiting effective amount of a denatured laminin selective antagonist to the patient.   
     
     
         26 . A method of detecting tumor cell adhesion in a patient comprising:
 administering a denatured laminin selective antagonist to the patient, and detecting bound denatured laminin selective antagonist in the patient.   
     
     
         27 . A method of treating a tumor in a patient comprising:
 administering a tumor cell adhesion-inhibiting effective amount of a denatured laminin selective antagonist to the patient.   
     
     
         28 . A method of treating metastasis in a patient comprising:
 administering a tumor cell adhesion-inhibiting effective amount of a denatured laminin selective antagonist to the patient.   
     
     
         29 . The method of  claim 25  wherein the denatured laminin selective antagonist is administered:
 intravenously, intraperitoneally, intramuscularly, subcutaneously, intracavity, transdermally, topically, intraocularly, orally, intranasally, or by peristaltic means.   
     
     
         30 . The method of  claim 25  wherein the denatured laminin selective antagonist dose range is 0.1 milligram per kilogram per day to 300 milligrams per kilogram per day. 
     
     
         31 . The method of  claim 25  wherein the denatured laminin selective antagonist dose range is 10 milligrams to 3000 milligrams. 
     
     
         32 . The method of  claim 27  wherein the denatured laminin selective antagonist is administered in combination with a chemotherapeutic agent, a radioactive material, or a cytostatic agent. 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . The method of  claim 25  wherein the patient is a mammal. 
     
     
         36 . The method of  claim 25  wherein the patient is a human. 
     
     
         37 . The method of  claim 12 , wherein said denatured laminin selective antagonist is a peptide, said peptide comprising an amino acid sequence selected from the following group: L-S-L-T-V; at least one conservative amino acid substitution of the amino acid sequence L-S-L-T-V; L-S-L-I—V; and at least one conservative amino acid substitution of the amino acid sequence L-S-L-I—V. 
     
     
         38 . The method of  claim 37 , wherein said denatured laminin selective antagonist comprises an amino acid sequence selected from the following group: NH 2 —S-T-Q-N-A-S-L-L-S-L-T-V—C—COOH (SEQ ID NO 1); NH 2 —K-G-G-C—S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 2), and NH 2 —K-G-G-S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 3). 
     
     
         39 . The method of  claim 13 , wherein said denatured laminin selective antagonist is a peptide, said peptide comprising an amino acid sequence selected from the following group: L-S-L-T-V; at least one conservative amino acid substitution of the amino acid sequence L-S-L-T-V; L-S-L-I—V; and at least one conservative amino acid substitution of the amino acid sequence L-S-L-I—V. 
     
     
         40 . The method of  claim 39 , wherein said denatured laminin selective antagonist comprises an amino acid sequence selected from the following group: NH 2 —S-T-Q-N-A-S-L-L-S-L-T-V—C—COOH (SEQ ID NO 1); NH 2 —K-G-G-C—S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 2), and NH 2 —K-G-G-S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 3). 
     
     
         41 . The method of  claim 14 , wherein said denatured laminin selective antagonist is a peptide, said peptide comprising an amino acid sequence selected from the following group: L-S-L-T-V; at least one conservative amino acid substitution of the amino acid sequence L-S-L-T-V; L-S-L-I—V; and at least one conservative amino acid substitution of the amino acid sequence L-S-L-I—V. 
     
     
         42 . The method of  claim 41 , wherein said denatured laminin selective antagonist comprises an amino acid sequence selected from the following group: NH 2 —S-T-Q-N-A-S-L-L-S-L-T-V—C—COOH (SEQ ID NO 1); NH 2 —K-G-G-C—S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 2), and NH 2 —K-G-G-S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 3). 
     
     
         43 . The method of  claim 15 , wherein said denatured laminin selective antagonist is a peptide, said peptide comprising an amino acid sequence selected from the following group: L-S-L-T-V; at least one conservative amino acid substitution of the amino acid sequence L-S-L-T-V; L-S-L-I—V; and at least one conservative amino acid substitution of the amino acid sequence L-S-L-I—V. 
     
     
         44 . The method of  claim 43 , wherein said denatured laminin selective antagonist comprises an amino acid sequence selected from the following group: NH 2 —S-T-Q-N-A-S-L-L-S-L-T-V—C—COOH (SEQ ID NO 1); NH 2 —K-G-G-C—S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 2), and NH 2 —K-G-G-S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 3). 
     
     
         45 . The method of  claim 16 , wherein said denatured laminin selective antagonist is a peptide, said peptide comprising an amino acid sequence selected from the following group: L-S-L-T-V; at least one conservative amino acid substitution of the amino acid sequence L-S-L-T-V; L-S-L-I—V; and at least one conservative amino acid substitution of the amino acid sequence L-S-L-I—V. 
     
     
         46 . The method of  claim 45 , wherein said denatured laminin selective antagonist comprises an amino acid sequence selected from the following group: NH 2 —S-T-Q-N-A-S-L-L-S-L-T-V—C—COOH (SEQ ID NO 1); NH 2 —K-G-G-C—S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 2), and NH 2 —K-G-G-S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 3). 
     
     
         47 . The method of  claim 25 , wherein said denatured laminin selective antagonist is a peptide, said peptide comprising an amino acid sequence selected from the following group: L-S-L-T-V; at least one conservative amino acid substitution of the amino acid sequence L-S-L-T-V; L-S-L-I—V; and at least one conservative amino acid substitution of the amino acid sequence L-S-L-I—V. 
     
     
         48 . The method of  claim 37 , wherein said denatured laminin selective antagonist comprises an amino acid sequence selected from the following group: NH 2 —S-T-Q-N-A-S-L-L-S-L-T-V—C—COOH (SEQ ID NO 1); NH 2 —K-G-G-C—S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 2), and NH 2 —K-G-G-S-T-Q-N-A-Q-L-L-S-L-J-V-G-K-A-COOH (SEQ ID NO 3). 
     
     
         49 . The method of  claim 26 , wherein said denatured laminin selective antagonist is a peptide, said peptide comprising an amino acid sequence selected from the following group: L-S-L-T-V; at least one conservative amino acid substitution of the amino acid sequence L-S-L-T-V; L-S-L-I—V; and at least one conservative amino acid substitution of the amino acid sequence L-S-L-I—V. 
     
     
         50 . The method of  claim 39 , wherein said denatured laminin selective antagonist comprises an amino acid sequence selected from the following group: NH 2 —S-T-Q-N-A-S-L-L-S-L-T-V—C—COOH (SEQ ID NO 1); NH 2 —K-G-G-C—S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 2), and NH 2 —K-G-G-S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 3). 
     
     
         51 . The method of  claim 27 , wherein said denatured laminin selective antagonist is a peptide, said peptide comprising an amino acid sequence selected from the following group: L-S-L-T-V; at least one conservative amino acid substitution of the amino acid sequence L-S-L-T-V; L-S-L-I—V; and at least one conservative amino acid substitution of the amino acid sequence L-S-L-I—V. 
     
     
         52 . The method of  claim 41 , wherein said denatured laminin selective antagonist comprises an amino acid sequence selected from the following group: NH 2 —S-T-Q-N-A-S-L-L-S-L-T-V—C—COOH (SEQ ID NO 1); NH 2 —K-G-G-C—S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 2), and NH 2 —K-G-G-S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 3). 
     
     
         53 . The method of  claim 28 , wherein said denatured laminin selective antagonist is a peptide, said peptide comprising an amino acid sequence selected from the following group: L-S-L-T-V; at least one conservative amino acid substitution of the amino acid sequence L-S-L-T-V; L-S-L-I—V; and at least one conservative amino acid substitution of the amino acid sequence L-S-L-I—V. 
     
     
         54 . The method of  claim 43 , wherein said denatured laminin selective antagonist comprises an amino acid sequence selected from the following group: NH 2 —S-T-Q-N-A-S-L-L-S-L-T-V—C—COOH (SEQ ID NO 1); NH 2 —K-G-G-C—S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 2), and NH 2 —K-G-G-S-T-Q-N-A-Q-L-L-S-L-I—V-G-K-A-COOH (SEQ ID NO 3).