Open AccessMultivalent Interactions: Synthesis and Evaluation of Melanotropin Multimers—Tools for Melanoma Targeting
Author(s) -
Nabila Brabez,
Kara Saunders,
Kevin L. Nguyen,
Thanuja Jayasundera,
Craig Weber,
Ronald M. Lynch,
Gérard Chassaing,
Solange Lavielle,
Victor J. Hruby
Publication year - 2012
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml300312b
Subject(s) - internalization , dendrimer , chemistry , computational biology , in vivo , biophysics , binding selectivity , scaffold , small molecule , receptor , combinatorial chemistry , microbiology and biotechnology , biochemistry , biology , computer science , genetics , database
In order 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 analogs 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 the molecules confirming their potential as delivery agents.