Structural highlights
Publication Abstract from PubMed
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 selec-tivity. 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 alpha,alpha-Dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin Receptors.,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 J Med Chem. 2018 Apr 16. doi: 10.1021/acs.jmedchem.8b00488. PMID:29660981[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. Development of Macrocyclic Peptidomimetics Containing Constrained alpha,alpha-Dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin Receptors. J Med Chem. 2018 Apr 16. doi: 10.1021/acs.jmedchem.8b00488. PMID:29660981 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b00488
