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.

中文翻译：

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含有受约束的α，α-二烷基化氨基酸对人黑皮质素受体具有强效和选择性活性的大环拟肽的研究

我们报告了MT-II和SHU-9119的大环黑皮质素衍生物的开发，该修饰是通过修改循环尺寸并在闭环中结合受约束的氨基酸实现的。这项研究最终发现了新型激动剂/拮抗剂，具有前所未有的活性，为黑皮质素受体选择性难题增添了新的元素。最后，所得的19元和20元环代表用于设计进一步的治疗性配体作为黑皮质素系统选择性调节剂的合适框架。