Multivalent Interactions:
Synthesis and Evaluation of Melanotropin MultimersTools for
Melanoma Targeting
Nabila Brabez
Kara Saunders
Kevin
L. Nguyen
Thanuja Jayasundera
Craig Weber
Ronald M. Lynch
Gerard Chassaing
Solange Lavielle
Victor J. Hruby
10.1021/ml300312b.s001
https://acs.figshare.com/articles/journal_contribution/Multivalent_Interactions_Synthesis_and_Evaluation_of_Melanotropin_Multimers_Tools_for_Melanoma_Targeting/2453473
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.
2013-01-10 00:00:00
cell surface targets
imaging studies
overexpressed melanocortin receptors
delivery agents
multimeric analogues
Multivalent Interactions
Melanoma TargetingTo
Enhanced specificity
viability studies
activity results
micromolar concentrations
binding affinity