Peptides that selectively home to heart vasculature and related conjugates and methods
The present invention provides a variety of isolated peptides and peptidomimetics, which can be useful, for example, in constructing the conjugates of the invention or, where the peptide itself has biological activity, in unconjugated form as a therapeutic for treating any of a varirty of cardiovascular diseases as described below. Thus, the present invention provides an isolated peptide or peptidomimetic which has a length of less than 60 residues and includes the amino acid sequence CRPPR (SEQ ID NO: 1) or a peptidomimetic thereof. The invention further provides an isolated peptide or peptidomimetic which has a length of less than 60 residues and includes the amino acid sequence CARPAR (SEQ ID NO: 5) or a peptidomimetic thereof, or amino acid sequence CPKRPR (SEQ ID NO: 6) or a peptidomimtic thereof.
1. An isolated peptide which selectively homes to heart vasculature, wherein said isolated peptide comprises CGRKSKTVC (SEQ ID NO: 2).
2. The isolated peptide or peptidomimetic of claim 1 , wherein said peptide consists of the amino acid sequence CGRKSKTVC (SEQ ID NO: 2).
3. The isolated peptide of claim 1 , wherein said peptide has a length of less than 100 residues.
4. The isolated peptide of claim 1 , wherein said peptide has a length of less than 60 residues.
5. The isolated peptide of claim 1 , wherein said peptide has a length of less than 20 residues.
6. A conjugate comprising a therapeutic agent or a detectable moiety linked to a homing peptide that selectively homes to heart vasculature, said homing peptide comprising the amino acid sequence CGRKSKTVC (SEQ ID NO: 2).
7. The conjugate of claim 6 , wherein said homing peptide consists of the amino acid sequence CGRKSKTVC (SEQ ID NO: 2).
8. The conjugate of claim 6 , wherein said homing peptide has a length of less than 100 residues.
9. he conjugate of claim 6 , wherein said homing peptide has a length of less than 60 residues.
10. The conjugate of claim 6 , wherein said homing peptide has a length of less than 20 residues.
11. The conjugate of claim 6 , wherein said conjugate comprises a therapeutic agent linked to said homing peptide.
12. The conjugate of claim 11 , wherein said therapeutic agent is selected from the group consisting of angiogenic agent, anti-thrombotic agent, anti-inflammatory agent, immunosuppressive agent, anti-arrhythmic agent, tumor necrosis factor inhibitor, endothelin inhibitor, angiotensin-converting enzyme (ACE) inhibitor, calcium antagonist, antibiotic agent, antiviral agent and viral vector.
13. The conjugate of claim 11 , wherein said therapeutic agent is an angiogenic agent.
14. The conjugate of claim 11 , wherein said therapeutic agent is an anti-thrombotic agent.
15. The conjugate of claim 6 , wherein said conjugate comprises a detectable moiety linked to said homing peptide.
16. The conjugate of claim 15 , wherein said detectable moiety is a paramagnetic ion, a radionuclide or a fluorescent molecule.