Melanocortin 1 receptor ligands and methods of use
The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.
1. A modified melanocortin 1 receptor (MC1R) peptide ligand, comprising an MC1R peptide ligand comprising 4-phenylbutyryl-His-DPhe-Arg-Trp (SEQ ID NO:6); and a functional group coupled to the C-terminus of said MC 1R peptide ligand.
2. The modified MC1R peptide ligand of claim 1 , wherein said functional group is an alkyne, azide, amine, aldehyde, thiol, alkene, ester, or maleimide.
3. A modified melanocortin 1 receptor (MC1R) peptide ligand selected from:
(SEQ ID NO: 3)
4-phenylbutyryl-His-DPhe-Arg-Trp-Gly-Lys(hex-5-
ynoyl)-NH 2 ;
(SEQ ID NO: 4)
H-Lys(hex-5-ynoyl)-Tyr-Val-Nle-Gly-His-DNal(2′)-
Arg-DTrp-Asp-Arg-Phe-Gly-NH 2 ;
or
(SEQ ID NO: 5)
H-Lys(hex-5-ynoyl)Tyr-Val-Nle-Gly-His-DNal(2′)-
Arg-DPhe-Asp-Arg-Phe-Gly-NH 2 .
4. The modified MC1R peptide ligand of claim 1 , wherein said functional group comprises a contrast agent.
5. The modified MC1R peptide ligand of claim 1 , wherein said functional group comprises a magnetic resonance imaging (MRI), single photon emission tomography (SPECT), or computed tomography (CT) contrast agent.
6. The modified MC1R peptide ligand of claim 4 , wherein said contrast agent comprises gadolinium (Gd) chelate, technetium (Tc99m) chelate, or 111 In chelate.
7. The modified MC1R peptide ligand of claim 4 , wherein said contrast agent comprises a fluorescent dye.
8. The modified MC1R peptide ligand of claim 1 , wherein said functional group comprises a chemotherapeutic agent.
9. The modified MC1R peptide ligand of claim 1 , wherein said functional group comprises an immunotherapeutic agent.
10. The modified MC1R peptide ligand of claim 1 , wherein said functional group comprises a polymer.
11. The modified MC1R peptide ligand of claim 1 , wherein said functional group comprises a particle.
12. The modified MC1R peptide ligand of claim 1 , wherein said functional group comprises a radiotherapy agent.
13. The modified MC1R peptide ligand of claim 1 , wherein said functional group comprises a radionuclide.
14. The MC1R peptide ligand of claim 3 , wherein said MC1R peptide ligand is said 4-phenylbutyryl-His-DPhe-Arg-Trp-Gly-Lys(hex-5-ynoyl)-NH 2 (SEQ ID NO:3).
15. The MC peptide ligand of claim 3 , wherein said MC1R peptide ligand is said H-Lys(hex-5-ynoyl)-Tyr-Val-Nle-Gly-His-DNal(2′)-Arg-DTrp-Asp-Arg-Phe-Gly-NH 2 (SEQ ID NO:4).
16. The MC1R peptide ligand of claim 3 , wherein said MC1R peptide ligand is said H-Lys(hex-5-ynoyl)Tyr-Val-Nle-Gly-His-DNal(2′)-Arg-DPhe-Asp-Arg-Phe-Gly-NH2 (SEQ ID NO:5).