Development of Macrocyclic Peptidomimetics Containing Constrained α,α-Dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin Receptors

Francesco Merlino, Yang Zhou, Minying Cai, Alfonso Carotenuto, Ali M. Yousif, Diego Brancaccio, Salvatore Di Maro, Silvia Zappavigna, Antonio Limatola, Ettore Novellino, Paolo Grieco, Victor J Hruby

Research output: Contribution to journalArticle

Abstract

We report the development of macrocyclic melanocortin derivatives of MT-II and SHU-9119, achieved by modifying the cycle dimension and incorporating constrained amino acids in ring-closing. This study culminated in the discovery of novel agonists/antagonists with an unprecedented activity profile by adding pieces to the puzzle of the melanocortin receptor selectivity. Finally, the resulting 19- and 20-membered rings represent a suitable frame for the design of further therapeutic ligands as selective modulators of the melanocortin system.

Original languageEnglish (US)
Pages (from-to)4263-4269
Number of pages7
JournalUnknown Journal
Volume61
Issue number9
DOIs
StatePublished - May 10 2018

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Merlino, F., Zhou, Y., Cai, M., Carotenuto, A., Yousif, A. M., Brancaccio, D., Di Maro, S., Zappavigna, S., Limatola, A., Novellino, E., Grieco, P., & Hruby, V. J. (2018). Development of Macrocyclic Peptidomimetics Containing Constrained α,α-Dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin Receptors. Unknown Journal, 61(9), 4263-4269. https://doi.org/10.1021/acs.jmedchem.8b00488