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Development of melanoma-targeted polymer micelles by conjugation of a melanocortin 1 receptor (MC1R) specific ligand.

Abstract：

:The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. Because of its high expression on the surface of melanomas, MC1R has been investigated as a target for selective imaging and therapeutic agents against melanoma. Eight ligands were screened against cell lines engineered to overexpress MC1R, MC4R, or MC5R. Of these, compound 1 (4-phenylbutyryl-His-dPhe-Arg-Trp-NH(2)) exhibited high (0.2 nM) binding affinity for MC1R and low (high nanomolar) affinities for MC4R and MC5R. Functionalization of the ligand at the C-terminus with an alkyne for use in Cu-catalyzed click chemistry was shown not to affect the binding affinity. Finally, formation of the targeted polymer, as well as the targeted micelle formulation, also resulted in constructs with low nanomolar binding affinity.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Barkey NM,Tafreshi NK,Josan JS,De Silva CR,Sill KN,Hruby VJ,Gillies RJ,Morse DL,Vagner J

doi

10.1021/jm201226w

subject

Has Abstract

pub_date

2011-12-08 00:00:00

pages

8078-84

issue

23

eissn

0022-2623

issn

1520-4804

journal_volume

54

pub_type

杂志文章

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