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.

Development of Macrocyclic Peptidomimetics Containing Constrained α,α-Dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin Receptors / Merlino, Francesco; Zhou, Yang; Cai, Minying; Carotenuto, Alfonso; Yousif, Ali M; Brancaccio, Diego; Di Maro, Salvatore; Zappavigna, Silvia; Limatola, Antonio; Novellino, Ettore; Grieco, Paolo; Hruby, Victor J. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - (2018). [10.1021/acs.jmedchem.8b00488]

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

Merlino, Francesco
Co-primo
;
Carotenuto, Alfonso;Yousif, Ali M;Brancaccio, Diego;Di Maro, Salvatore;Limatola, Antonio;Novellino, Ettore;Grieco, Paolo
;
2018

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.
2018
Development of Macrocyclic Peptidomimetics Containing Constrained α,α-Dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin Receptors / Merlino, Francesco; Zhou, Yang; Cai, Minying; Carotenuto, Alfonso; Yousif, Ali M; Brancaccio, Diego; Di Maro, Salvatore; Zappavigna, Silvia; Limatola, Antonio; Novellino, Ettore; Grieco, Paolo; Hruby, Victor J. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - (2018). [10.1021/acs.jmedchem.8b00488]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/717817
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