Molecules that selectively home to vasculature of pre-malignant dysplastic lesions or malignancies
View Patent ↗The present invention provides a conjugate that contains a therapeutic moiety linked to a homing peptide or peptidomimetic which selectively homes to vasculature of pre-malignant dysplastic skin and which includes the amino acid sequence SRPRR (SEQ ID NO: 1) or a conservative variant or peptidomimetic thereof. The present invention further provides a conjugate containing a therapeutic moiety linked to a homing peptide or peptidomimetic which selectively homes to vasculature of malignant skin and which includes the amino acid sequence CGKRK (SEQ ID NO: 6) or the amino acid sequence CDTRL (SEQ ID NO: 7), or a conservative variant or peptidomimetic of one of these sequences.
1. A conjugate, comprising a moiety linked to a homing peptide that selectively homes to vasculature of pre-malignant dysplastic skin, wherein said homing peptide comprises the amino acid sequence CXSRPRRZC (SEQ ID NO: 2)
wherein X=0 to 20 independently selected residues and
wherein Z=0 to 20 independently selected residues.
2. An isolated peptide, having a length of less than 45 residues and comprising the amino acid sequence CXSRPRRZC (SEQ ID NO: 2),
wherein X=0 to 20 independently selected residues and
wherein Z=0 to 20 independently selected residues.
3. The isolated peptide of claim 2 , which is conformationally constrained.
4. The isolated peptide of claim 3 , which is cyclic.
5. The conjugate of claim 1 , wherein said moiety is a therapeutic moiety.
6. The conjugate of claim 5 , wherein said therapeutic moiety is an antiangiogenic agent.
7. The conjugate of claim 5 , wherein said therapeutic moiety is a cytotoxic agent.
8. The conjugate of claim 1 , wherein said moiety is a detectable moiety.
9. The conjugate of claim 8 , wherein said detectable moiety is a radionuclide.
10. The conjugate of claim 8 , wherein said detectable moiety is a fluorescent label.
11. The conjugate of claim 1 , wherein the peptide comprises the amino acid sequence CSRPRRSEC (SEQ ID NO: 3).
12. The conjugate of claim 1 , wherein the peptide comprises the amino acid sequence CSRPRRSVC (SEQ ID NO: 4).
13. The conjugate of claim 1 , wherein the peptide comprises the amino acid sequence CSRPRRSWC (SEQ ID NO: 5).
14. The isolated peptide of claim 2 , wherein the peptide has a length of less than 40 residues.
15. The isolated peptide of claim 2 , wherein the peptide has a length of less than 35 residues.
16. The isolated peptide of claim 2 , wherein the peptide has a length of less than 30 residues.
17. The isolated peptide of claim 2 , wherein the peptide has a length of less than 25 residues.
18. The isolated peptide of claim 2 , wherein the peptide has a length of less than 20 residues.
19. The isolated peptide of claim 2 , wherein the peptide has a length of less than 15 residues.
20. The isolated peptide of claim 2 , wherein the peptide has a length of less than 12 residues.
21. The isolated peptide of claim 2 , wherein the peptide has a length of less than 10 residues.
22. The isolated peptide of claim 2 , wherein the peptide has a length of less than 9 residues.
23. The isolated peptide of claim 2 , wherein the peptide comprises the amino acid sequence CSRPRRSEC (SEQ ID NO: 3).
24. The isolated peptide of claim 2 , wherein the peptide comprises the amino acid sequence CSRPRRSVC (SEQ ID NO: 4).
25. The isolated peptide of claim 2 , wherein the peptide comprises the amino acid sequence CSRPRRSWC (SEQ ID NO: 5).
26. An isolated cyclic peptide having a length of less than 90 residues and comprising the amino acid sequence CXSRPRRZC (SEQ ID NO: 2),
wherein X=0 to 20 independently selected residues and wherein Z=0 to 20 independently selected residues.
27. The isolated peptide of claim 26 , wherein the peptide has a length of less than 80 residues.
28. The isolated peptide of claim 26 , wherein the peptide has a length of less than 70 residues.
29. The isolated peptide of claim 26 , wherein the peptide has a length of less than 60 residues.
30. The isolated peptide of claim 26 , wherein the peptide has a length of less than 50 residues.
31. The isolated peptide of claim 26 , wherein the peptide has a length of less than 45 residues.
32. The isolated peptide of claim 26 , wherein the peptide has a length of less than 40 residues.
33. The isolated peptide of claim 26 , wherein the peptide has a length of less than 35 residues.
34. The isolated peptide of claim 26 , wherein the peptide has a length of less than 30 residues.
35. The isolated peptide of claim 26 , wherein the peptide has a length of less than 25 residues.
36. The isolated peptide of claim 26 , wherein the peptide has a length of less than 20 residues.
37. The isolated peptide of claim 26 , wherein the peptide has a length of less than 15 residues.
38. The isolated peptide of claim 26 , wherein the peptide has a length of less than 12 residues.
39. The isolated peptide of claim 26 , wherein the peptide has a length of less than 10 residues.
40. The isolated peptide of claim 26 , wherein the peptide has a length of less than 9 residues.
41. The isolated peptide of claim 26 , wherein the peptide comprises the amino acid sequence CSRPRRSEC (SEQ ID NO: 3).
42. The isolated peptide of claim 26 , wherein the peptide comprises the amino acid sequence CSRPRRSVC (SEQ ID NO: 4).
43. The isolated peptide of claim 26 , wherein the peptide comprises the amino acid sequence CSRPRRSWC (SEQ ID NO: 5).