Melanocortin receptors are pharmaceutically important receptors that are involved in complex physiological functions. They have been associated with various diseases including obesity, erectile dysfunction, acne, and skin cancer. It has been challenging to transform nonselective endogenous agonist and antagonist ligands into selective and potent ligands. In this study, we investigated naturally occurring peptides derived from frog skin secretions for selectivity and activity toward melanocortin receptors. Three peptides (ORB, ORB2K and ranacyclin-T) were found to have selectivity towards the melanocortin receptor 5 (MC5R). ORB and ORB2K had partial binding affinity at nanomolar concentrations, whereas ranacyclin-T had 57% binding efficiency at 1.6 μM. Backbone cyclization of ORB and ORB2K altered the binding efficiency to melanocortin receptors. Our results suggest that these frog-skin peptides could be modified for developing melanocortin-specific ligands and potentially future therapeutics.

中文翻译：

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开发对黑皮质素受体亚型具有选择性的新型蛙皮肽支架

黑皮质素受体是涉及复杂生理功能的药学上重要的受体。它们与多种疾病有关，包括肥胖、勃起功能障碍、痤疮和皮肤癌。将非选择性内源性激动剂和拮抗剂配体转化为选择性和有效的配体一直具有挑战性。在这项研究中，我们研究了源自青蛙皮肤分泌物的天然肽对黑皮质素受体的选择性和活性。发现三种肽（ORB、ORB2K 和雷那环素-T）对黑皮质素受体 5 (MC5R) 具有选择性。ORB 和 ORB2K 在纳摩尔浓度下具有部分结合亲和力，而雷那环素-T 在 1.6 μM 时具有 57% 的结合效率。ORB 和 ORB2K 的骨架环化改变了与黑皮质素受体的结合效率。