MOLECULES THAT SELECTIVELY HOME TO VASCULATURE OF PREMALIGNANT OR MALIGNANT LESIONS OF THE PANCREAS AND OTHER ORGANS
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)