title: Multivalent Interactions: Synthesis and Evaluation of Melanotropin Multimers - Tools for Melanoma Targeting.
abstract: 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 targetsviathe 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 usedin vivo. Finally, imaging studies showed effective internalization for all the molecules confirming their potential as delivery agents.
authors.affiliation: UPMC Paris 06, UMR 7203, Laboratoire des BioMolécules, Université P. et M. Curie, 75005 Paris France ; CNRS, UMR 7203, France ; ENS, UMR 7203, Département de Chimie, Ecole Normale Supérieure, 75005 Paris France ; University of Arizona, Department of Chemistry and Biochemistry, Tucson, AZ 85721, USA.
authors.forename: Nabila
authors.initials: N
authors.lastname: Brabez
authors.forename: Kara
authors.initials: K
authors.lastname: Saunders
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Nguyen
authors.forename: Thanuja B M
authors.initials: TB
authors.lastname: Jayasundera
authors.forename: Craig
authors.initials: C
authors.lastname: Weber
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Lynch
authors.forename: Gerard
authors.initials: G
authors.lastname: Chassaing
authors.forename: Solange
authors.initials: S
authors.lastname: Lavielle
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
keywords: Multivalent interactions; cancer; delivery; dendrimers; melanoma; multimers; peptides; targeted therapy