Methods and compositions related to internalizing RGD peptides
Disclosed are compositions and methods useful for targeting tissue undergoing angiogenesis or to cells or tissue expressing αv integrins. The compositions and methods are based on peptide sequences that selectively bind to and home to tissue undergoing angiogenesis or to cells or tissue expressing αv integrins in animals. The disclosed targeting is useful for delivering therapeutic and detectable agents to tissue experiencing angiogenesis or to cells or tissue expressing αv integrins.
1. An isolated peptide comprising an amino acid segment comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO:290, one of the amino acid sequences CRGD(R/K/H)GV(D/E/H)C (SEQ ID NO:329), or one of the amino acid sequences CRGDHGP(D/E/H)C (SEQ ID NO:330) consisting of one, two, or three conservative amino acid substitutions.
2. The isolated peptide of claim 1 , wherein the peptide has a length of less than 100 residues.
3. The isolated peptide of claim 1 , wherein the peptide has a length of less than 50 residues.
4. The isolated peptide of claim 1 , wherein the peptide has a length of less than 20 residues.
5. The isolated peptide of claim 1 , wherein the amino acid segment is cyclic.
6. The isolated peptide of claim 5 , wherein the amino acid segment is cyclized via a disulfide bond.
7. The isolated peptide of claim 1 , wherein the peptide selectively homes to a site of angiogenesis.
8. The isolated peptide of claim 7 , wherein the angiogenesis is at a site of injury.
9. The isolated peptide of claim 7 , wherein the angiogenesis is at a surgical site.
10. The isolated peptide of claim 1 , wherein the peptide selectively homes to a tumor.
11. The isolated peptide of claim 1 , wherein the peptide selectively homes to a site of arthritis.
12. The isolated peptide of claim 1 , wherein the peptide selectively homes to a cell or tissue expressing one or more αv integrins.
13. The isolated peptide of claim 1 , wherein the peptide selectively homes to a cell or tissue expressing one or more av integrins and neuropilin-1.
14. The isolated peptide of claim 1 , wherein the peptide consists of the amino acid segment.
15. The isolated peptide of claim 1 , wherein the peptide consists of the amino acid sequence.
16. An isolated peptide comprising an amino acid segment comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO:290, one of the amino acid sequences CRGD(R/K/H)GV(D/E/H)C (SEQ ID NO:329), or one of the amino acid sequences CRGDHGP(D/E/H)C (SEQ ID NO:330) consisting of one, two, or three conservative amino acid substitutions, wherein the amino acid sequence comprises RGD.