N-alkylated dipeptide amides and related structures as imitations of the melanocortins' active core
2005 (English)In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 26, no 10, 1997-2016 p.Article in journal (Refereed) Published
Thirty-three low molecular mass structures combining both peptide and peptoid features were prepared and tested on human melanocortin receptors MC1,3-5R. Most of them displayed low micromolar activity with preference for diamines, guanidino and 2-naphthyl derivatives compared to monoacetylated, amino and 3-indolyl counterparts. Some contained L- or D-histidine residues, but the change did not influence affinity. QSAR modelling yielded excellent models for the MC3-5 receptors explaining R2Y=0.89-0.91 and predicting Q2=0.77-0.80 of the affinity variations. One compound displayed MC1R selectivity (13-fold and more). An NMR study of showed that it exists as a mixture of four rotamers at its tertiary amide bonds. Comparisons with earlier data for melanocortin core tetrapeptide analogues indicate that the novel peptide-peptoids interact with the melanocortin receptors in a different way.
Place, publisher, year, edition, pages
2005. Vol. 26, no 10, 1997-2016 p.
Melanocortins, Peptidomimetics, Peptoid–peptide hybrids, Solid phase organic synthesis, Structure–activity, QSAR, NMR
IdentifiersURN: urn:nbn:se:uu:diva-104278DOI: 10.1016/j.peptides.2004.11.026PubMedID: 15985308OAI: oai:DiVA.org:uu-104278DiVA: diva2:219588