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

doi: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

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 journal › Article › peer-review

13 Scopus citations

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 language	English (US)
Pages (from-to)	4263-4269
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	61
Issue number	9
DOIs	https://doi.org/10.1021/acs.jmedchem.8b00488
State	Published - May 10 2018

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/acs.jmedchem.8b00488

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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. Journal of Medicinal Chemistry, 61(9), 4263-4269. https://doi.org/10.1021/acs.jmedchem.8b00488

Merlino, F, Zhou, Y, Cai, M, Carotenuto, A, Yousif, AM, Brancaccio, D, Di Maro, S, Zappavigna, S, Limatola, A, Novellino, E, Grieco, P & Hruby, VJ 2018, 'Development of Macrocyclic Peptidomimetics Containing Constrained α,α-Dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin Receptors', Journal of Medicinal Chemistry, vol. 61, no. 9, pp. 4263-4269. https://doi.org/10.1021/acs.jmedchem.8b00488

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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.",

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

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doi = "10.1021/acs.jmedchem.8b00488",

language = "English (US)",

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AU - Merlino, Francesco

AU - Zhou, Yang

AU - Cai, Minying

AU - Carotenuto, Alfonso

AU - Yousif, Ali M.

AU - Brancaccio, Diego

AU - Di Maro, Salvatore

AU - Zappavigna, Silvia

AU - Limatola, Antonio

AU - Novellino, Ettore

AU - Grieco, Paolo

AU - Hruby, Victor J.

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AB - 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.

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

Abstract

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NMR ensemble of Macrocyclic Peptidomimetic Containing Constrained a,a-dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin Receptors

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

Abstract

ASJC Scopus subject areas

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Datasets

NMR ensemble of Macrocyclic Peptidomimetic Containing Constrained a,a-dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin Receptors

Cite this