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Novel targeting strategy based on multimeric ligands for drug delivery and molecular imaging: homooligomers of alpha-MSH.

Abstract：

:Homooligomers constructed with 4- and 6-amino acid fragments of melanocortin (alpha-MSH) bind with higher affinity and with apparent cooperativity to melanocortin receptor, compared to their constituent monomers. Individual ligands were tethered with various spacers of different length and rigidity and the influence of spacers on binding was studied. Binding assays were performed on cells transfected with the melanocortin receptor, hMC4R. There is a 5-7-fold decrease in the EC(50) with the addition of each subunit, going from monomer to trimer. The Hill coefficient increases from 0.76 for the monomer to 1.12 for the dimer and 1.35 for the trimer. These data show a general trend of increasing avidity with increasing number of ligands in oligomers.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Vagner J,Handl HL,Gillies RJ,Hruby VJ

doi

10.1016/j.bmcl.2003.09.079

subject

Has Abstract

pub_date

2004-01-05 00:00:00

pages

211-5

issue

1

eissn

0960-894X

issn

1464-3405

pii

S0960894X03010710

journal_volume

14

pub_type

杂志文章

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