Melanocortin 1 receptor ligands and methods of use

Patent metadata

Field	Value
Publication number	US-9441013-B2
Application number	US-201214117949-A
Country	US
Kind code	B2
Filing date	May 17, 2012
Priority date	May 17, 2011
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

Abstract

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.

First claim

We claim:

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).

Assignees

• Gillies Robert J
• Morse David L
• Barkey Natalie M
• Sill Kevin N
• Vagner Josef
• Tafreshi Narges K
• Sessler Jonathan L
• Preihs Christian
• Hruby Victor J
• H Lee Moffitt Cancer Ct & Res
• Intezyne Tech Inc
• Univ Arizona
• Board Of Regents Univ Of Texas System

Inventors

• Gillies Robert J
• Morse David L
• Barkey Natalie M
• Sill Kevin N
• Vagner Josef
• Tafreshi Narges K
• Sessler Jonathan L
• Preihs Christian
• Hruby Victor J

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K49/101

  the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals · CPC title

• C07K7/08 Primary

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• A61K47/6907

  the form being a microemulsion, nanoemulsion or micelle · CPC title

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title