Molecules that selectively home to vasculature of premalignant or malignant lesions of the pancreas and other organs

Abstract

The invention provides a conjugate that includes a therapeutic moiety linked to a peptide or peptidomimetic that selectively homes to vasculature of premalignant pancreas. The peptide or peptidomimetic contains at least 5 contiguous amino acids of an amino acid sequence selected from CRSRKG (SEQ ID NO:9) and CEYQLDVE (SEQ ID NO:34), or a conservative variant or peptidomimetic thereof. The invention additionally provides a conjugate containing a therapeutic moiety linked to a peptide or peptidomimetic that selectively homes to pancreatic tumor cells and pancreatic tumor vasculature, the peptide or peptidomimetic comprising at least 5 contiguous amino acids of an amino acid sequence selected from CKAAKNK (SEQ ID NO:15), CKGAKAR (SEQ ID NO:19), and VGVGEWSV (SEQ ID NO:35), or a conservative variant or peptidomimetic thereof.

1 . A peptide or peptidomimetic, having a length of less than 60 amino acid residues and comprising at least 5 contiguous amino acids of an amino acid sequence selected from CKGAKAR (SEQ ID NO:19), FRVGVADV (SEQ ID NO:27), CEYQLDVE (SEQ ID NO:34) and VGVGEWSV (SEQ ID NO:35), or a conservative variant or peptidomimetic thereof. 
     
     
         2 . The peptide or peptidomimetic of  claim 1 , wherein said peptide or peptidomimetic is a peptide. 
     
     
         3 . The peptide or peptidomimetic of  claim 1 , having a length of less than 40 amino acid residues. 
     
     
         4 . The peptide or peptidomimetic of  claim 1 , having a length of less than 20 amino acid residues. 
     
     
         5 . The peptide or peptidomimetic of  claim 1 , having a length of less than 10 amino acid residues. 
     
     
         6 . A conjugate, comprising a therapeutic moiety linked to a peptide or peptidomimetic that selectively homes to vasculature of premalignant pancreas, said peptide or peptidomimetic comprising at least 5 contiguous amino acids of the amino acid sequence CEYQLDVE (SEQ ID NO:34), or a conservative variant or peptidomimetic thereof, or wherein said peptide or peptidomimetic binds specifically to a cognate receptor for SEQ ID NO:34. 
     
     
         7 . The conjugate of  claim 6 , wherein said peptide or peptidomimetic has a length of less than 100 residues. 
     
     
         8 . The conjugate of  claim 6 , wherein said peptide or peptidomimetic has a length of less than 50 residues. 
     
     
         9 . The conjugate of  claim 6 , wherein said peptide or peptidomimetic has a length of less than 25 residues. 
     
     
         10 . The conjugate of  claim 6 , wherein said peptide or peptidomimetic is a peptide. 
     
     
         11 - 22 . (canceled) 
     
     
         23 . A conjugate, comprising a therapeutic moiety linked to a peptide or peptidomimetic that selectively homes to pancreatic tumor cells and pancreatic tumor vasculature, said peptide or peptidomimetic comprising at least 5 contiguous amino acids of an amino acid sequence selected from CKGAKAR (SEQ ID NO:19) and VGVGEWSV (SEQ ID NO:35), or a conservative variant or peptidomimetic thereof, or wherein said peptide or peptidomimetic binds specifically to a cognate receptor for SEQ ID NO:19 or SEQ ID NO:35. 
     
     
         24 . The conjugate of  claim 23 , wherein said peptide or peptidomimetic has a length of less than 100 residues. 
     
     
         25 . The conjugate of  claim 23 , wherein said peptide or peptidomimetic has a length of less than 50 residues. 
     
     
         26 . The conjugate of  claim 23 , wherein said peptide or peptidomimetic has a length of less than 25 residues. 
     
     
         27 . The conjugate of  claim 23 , wherein said peptide or peptidomimetic is a peptide. 
     
     
         28 . (canceled) 
     
     
         29 . The conjugate of  claim 23 , wherein said peptide or peptidomimetic comprises at least 5 contiguous amino acids of CKGAKAR (SEQ ID NO:19) or a conservative variant or peptidomimetic thereof. 
     
     
         30 . The conjugate of  claim 23 , wherein said peptide or peptidomimetic comprises at least 5 contiguous amino acids of VGVGEWSV (SEQ ID NO:35) or a conservative variant or peptidomimetic thereof. 
     
     
         31 - 43 . (canceled) 
     
     
         44 . The conjugate of  claim 23 , wherein said therapeutic moiety is an angiogenic inhibitor. 
     
     
         45 . The conjugate of  claim 44 , wherein said angiogenic inhibitor is selective for mature tumor vasculature. 
     
     
         46 . The conjugate of  claim 23 , wherein said therapeutic moiety is a cytotoxic agent. 
     
     
         47 - 54 . (canceled) 
     
     
         55 . A conjugate, comprising a therapeutic moiety linked to a peptide or peptidomimetic that selectively homes to premalignant and malignant pancreatic vasculature, said peptide or peptidomimetic comprising at least 5 contiguous amino acids of an amino acid sequence selected from FRVGVADV (SEQ ID NO:27), or a conservative variant or peptidomimetic thereof, or wherein said peptide or peptidomimetic binds specifically to a cognate receptor for SEQ ID NO:27. 
     
     
         56 - 67 . (canceled) 
     
     
         68 . The conjugate of  claim 55 , wherein said peptide or peptidomimetic has a length of less than 100 residues. 
     
     
         69 . The conjugate of  claim 55 , wherein said peptide or peptidomimetic has a length of less than 50 residues. 
     
     
         70 . The conjugate of  claim 55 , wherein said peptide or peptidomimetic has a length of less than 25 residues. 
     
     
         71 . The conjugate of  claim 55 , wherein said peptide or peptidomimetic is a peptide. 
     
     
         72 . The conjugate of  claim 55 , wherein said therapeutic moiety is an angiogenic inhibitor. 
     
     
         73 . The conjugate of  claim 72 , wherein said angiogenic inhibitor is selective for mature tumor vasculature. 
     
     
         74 . The conjugate of  claim 55 , wherein said therapeutic moiety is a cytotoxic agent. 
     
     
         75 . A multivalent conjugate, comprising a therapeutic moiety linked to at least two peptides or peptidomimetics that selectively home to vasculature of premalignant pancreas, each of said peptides or peptidomimetics comprising at least 5 contiguous amino acids of the amino acid sequence CEYQLDVE (SEQ ID NO:34), or wherein each of said peptides or peptidomimetics binds specifically to a cognate receptor for SEQ ID NO:34;
 wherein said at least two peptides or peptidomimetics selectively home to pancreatic tumor cells and pancreatic tumor vasculature, each of said peptides or peptidomimetics comprising at least 5 contiguous amino acids of an amino acid sequence selected from CKGAKAR (SEQ ID NO:19), and VGVGEWSV (SEQ ID NO:35), or a conservative variant or peptidomimetic thereof, or wherein each of said peptides or peptidomimetics binds specifically to a cognate receptor for an amino acid sequence selected from CKGAKAR (SEQ ID NO:19) and VGVGEWSV (SEQ ID NO:35);   or wherein said at least two peptides or peptidomimetics selectively home to premalignant and malignant vasculature, each of said peptides or peptidomimetics comprising at least 5 contiguous amino acids of the amino acid sequence FRVGVADV (SEQ ID NO:27), or a conservative variant or peptidomimetic thereof, or wherein each of said peptides or peptidomimetics binds specifically to a cognate receptor for the amino acid sequence FRVGVADV (SEQ ID NO:27).   
     
     
         76 - 93 . (canceled)