Synthetic approach to designed chemical structures

Abstract

This invention relates to the chemical design and production of peptides, peptide structure and three dimensional conformation was assessed using NMR, circular dichroisin and pulsed field gradient NMR.

1 - 20 . (canceled)  
     
     
         21 . A water soluble peptide selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30).  
     
     
         22 . A method for treating a bacteria infection or endotoxic shock comprising administering to a mammal an amount of a pharmaceutical composition effective to inhibit the bacterial infection or neutralize endotoxin, wherein the pharmaceutical composition comprises: 
 (a) a peptide demonstrating bactericidal activity or endotoxin neutralizing activity selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30); and    (b) a pharmaceutically acceptable carrier.    
     
     
         23 . The method of  claim 22  wherein the peptide neutralizes endotoxin.  
     
     
         24 . The method of  claim 22  wherein the peptide is bactericidal.  
     
     
         25 . The method of  claim 22  wherein the peptide is both bactericidal and neutralizes endotoxin.  
     
     
         26 . The method of  claim 22  wherein the peptide has endotoxin neutralizing activity and is selected from the group consisting of βpep-8 and βpep-23.  
     
     
         27 . The method of  claim 22  wherein the peptide has bactericidal activity and is selected from the group consisting of βpep-19, βpep-7, βpep-4, βpep-22 and βpep-1.  
     
     
         28 . A method for inhibiting TNF-α levels in a mammal comprising administering a therapeutically effective amount of a pharmaceutical composition comprising: 
 (a) a peptide demonstrating bactericidal activity or endotoxin neutralizing activity selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30); and    (b) a pharmaceutically acceptable carrier.    
     
     
         29 . The method of  claim 28  wherein the peptide is βpep-3.  
     
     
         30 . A method for inhibiting endothelial cell proliferation comprising administering to a mammal an effective amount of a composition comprising: 
 a peptide demonstrating endothelial cell proliferation inhibition selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30).    
     
     
         31 . The method of  claim 30  wherein the composition is a therapeutically effective amount of a pharmaceutical composition comprising: 
 (a) a peptide selected from the group consisting of βpep-14 or βpep-16; and    (b) a pharmaceutically acceptable carrier.    
     
     
         32 . A method for promoting inter-cellular adhesion molecule expression comprising administering to a mammal an effective amount of a composition comprising: 
 a peptide promoting inter-cellular adhesion molecule expression selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30).    
     
     
         33 . A method for inhibiting angiogenesis in a cell culture, the method comprising contacting cells with an effective amount of a composition comprising a peptide selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30).  
     
     
         34 . A method for inhibiting angiogenesis in a mammal, the method comprising administering to the mammal an effective amount of a composition comprising a peptide selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30); and a pharmaceutically acceptable carrier.  
     
     
         35 . A method for inhibiting tumorigenesis in a mammal, the method comprising administering to the mammal an effective amount of a composition comprising a peptide selected from the group consisting of βpep- 1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30) and a pharmaceutically acceptable carrier.  
     
     
         36 . A method for inhibiting bacterial infection or endotoxic shock in a cell culture, the method comprising contacting cells with an effective amount of a composition comprising a peptide selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30).  
     
     
         37 . A method for inhibiting TNF-α levels in a cell culture, the method comprising contacting cells with an effective amount of a composition comprising a peptide selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30).  
     
     
         38 . A method for inhibiting endothelial cell proliferation in a cell culture, the method comprising contracting cells with an effective amount of a composition comprising: 
 a peptide demonstrating endothelial cell proliferation inhibition selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30).    
     
     
         39 . A method for promoting inter-cellular adhesion molecule expression in a cell culture, the method comprising contacting cells with an effective amount of a composition comprising: 
 a peptide promoting inter-cellular adhesion molecule expression selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30).    
     
     
         40 . A method for inhibiting inter-cellular adhesion molecule expression down regulation in a mammal, the method comprising administering to the mammal an effective amount of a composition comprising: 
 a peptide inhibiting inter-cellular adhesion molecule expression down regulation selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30).    
     
     
         41 . A method for inhibiting inter-cellular adhesion molecule expression down regulation in a cell culture, the method comprising contacting cells with an effective amount of a composition comprising: 
 a peptide inhibiting inter-cellular adhesion molecule expression down regulation selected from the group consisting of βpep-1 through βpep-18 and βpep 20 through βpep-24 and βpep 26 through βpep-30 (SEQ ID NOS: 1-18 and 20-24 and 26-30).    
     
     
         42 . The peptide of  claim 21  further comprising a pharmaceutically acceptable carrier.  
     
     
         43 . The peptide of  claim 42  wherein said pharmaceutically acceptable carrier is selected from the group consisting of isotonic saline, dimethylsulfoxide, alcohol, phosphate buffered saline, and other balanced salt solutions.  
     
     
         44 . The peptide of  claim 21  conjugated to a protein carrier.  
     
     
         45 . The peptide of  claim 44  wherein said protein carrier is selected from the group consisting of keyhole limpet hemocyanin (KLH), bovine serum albumin (BSA), and ovalbumin.  
     
     
         46 . A method for inhibiting leukocyte/endothelial cell adhesion in a cell culture, the method comprising contacting cells with an effective amount of a composition comprising a peptide selected from the group consisting of βpep-1 through βpep-30 (SEQ ID NOS: 1-30).  
     
     
         47 . A method of increasing leukocyte cell infiltration in a mammal, the method comprising administering to the mammal an effective amount of a composition comprising a peptide selected from the group consisting of βpep-1 through βpep-30 (SEQ ID NOS: 1-30); and a pharmaceutically acceptable carrier.