title: Synthesis and bioactivity of MSH4 oligomers prepared by an A2+ B2strategy.
abstract: Oligomers incorporating the tetrapeptide MSH4, the minimum active sequence of melanocyte stimulating hormone, were synthesized by an A2+ B2strategy involving microwave-assisted copper-catalyzed azide-alkyne cycloaddition. A2contained an MSH4 core while B2contained a (Pro-Gly)3spacer. Soluble mixtures containing compounds with up to eight MSH4 units were obtained from oligomerizations at high monomer concentrations. The avidities of several oligomeric mixtures were evaluated by means of a competitive binding assay using HEK293 cells engineered to overexpress the melanocortin 4 receptor. When based on total MSH4 concentrations, avidities were only minimally enhanced compared with a monovalent control. The lack of variation in the effect of ligands on probe binding is consistent with high off rates for MSH4 in both monovalent and oligomeric constructs relative to that of the competing probe.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721-0041, USA.
authors.forename: Dilani Chathurika
authors.initials: DC
authors.lastname: Dehigaspitiya
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721-0041, USA.
authors.forename: Suryakiran
authors.initials: S
authors.lastname: Navath
authors.affiliation: Department of Physiology, University of Arizona, Tucson, AZ 85724-5051, USA.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Weber
authors.affiliation: Department of Physiology, University of Arizona, Tucson, AZ 85724-5051, USA ; The Bio5 Institute, University of Arizona, Tucson, AZ 85721-0240, USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Lynch
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721-0041, USA.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Mash
keywords: Competitive binding assay; Melanocortin 4 receptor; Multivalent ligand; Oligomerization; Time-resolved fluorescence