Multivalent interactions: Synthesis and evaluation of melanotropin multimers - Tools for melanoma targeting

Nabila Brabez, Kara Saunders, Kevin L. Nguyen, Thanuja Jayasundera, Craig Weber, Ronald M. Lynch, Gerard Chassaing, Solange Lavielle, Victor J. Hruby

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

To develop agents for early detection and selective treatment of melanomas, high affinity and high specificity molecular tools are required. Enhanced specificity may be obtained by simultaneously binding to multiple cell surface targets via the use of multimeric analogues of naturally occurring ligands. Trimers targeting overexpressed melanocortin receptors have been found to be potential candidates for this purpose. In the present letter, we describe the synthesis and study of multimers based on a dendrimer-like scaffold. The binding affinity and activity results revealed that dendrimers promote multivalent interactions via statistical and/or cooperative effects on binding. Moreover, viability studies showed no significant toxicity at micromolar concentrations, which will allow these molecular complexes to be used in vivo. Finally, imaging studies showed effective internalization for all of the molecules, confirming their potential as delivery agents.

Original languageEnglish (US)
Pages (from-to)98-102
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume4
Issue number1
DOIs
StatePublished - Jan 10 2013

Keywords

  • cancer
  • delivery
  • dendrimers
  • melanoma
  • multimers
  • multivalent interactions
  • peptides
  • targeted therapy

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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