1229615-57-9Relevant articles and documents
Multiple N -methylation of MT-II backbone amide bonds leads to melanocortin receptor subtype hMC1R selectivity: Pharmacological and conformational studies
Doedens, Lucas,Opperer, Florian,Cai, Minying,Beck, Johannes G.,Dedek, Matt,Palmer, Erin,Hruby, Victor J.,Kessler, Horst
experimental part, p. 8115 - 8128 (2010/08/13)
Multiple N-methylation is a novel technology to improve bioavailability of peptides and increase receptor subtype selectivity. This technique has been applied here to the superpotent but nonselective cyclic peptide MT-II. A library of all possible 31 backbone N-methylated derivatives has been synthesized and tested for binding and activation at melanocortin receptor subtypes 1, 3, 4, and 5. It turned out that selectivity is improved with every introduced N-methyl group, resulting in several N-methylated selective and potent agonists for the hMC1R. The most potent of these derivatives is N-methylated on four out of five amide bonds in the cyclic structure. Its solution structure indicates a strongly preferred backbone conformation that resembles other α-MSH analogs but possesses much less flexibility and in addition distinct differences in the spatial arrangement of individual amino acid side chains.
