Effects of C-Terminal B-Chain Modifications in a Relaxin 3 Agonist Analogue,ACS Medicinal Chemistry Letters

当前位置： X-MOL 学术 › ACS Med. Chem. Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Effects of C-Terminal B-Chain Modifications in a Relaxin 3 Agonist Analogue
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2020-10-22 , DOI: 10.1021/acsmedchemlett.0c00456
Praveen Praveen ₁ , Julien Tailhades _{2,

3} , K Johan Rosengren ₄ , Mengjie Liu ₁ , John D Wade _{1,

5} , Ross A D Bathgate _{1,

5} , Mohammed Akhter Hossain _{1,

5}

Affiliation

The receptor for the neuropeptide relaxin 3, relaxin family peptide 3 (RXFP3) receptor, is an attractive pharmacological target for the control of eating, addictive, and psychiatric behaviors. Several structure–activity relationship studies on both human relaxin 3 (containing 3 disulfide bonds) and its analogue A2 (two disulfide bonds) suggest that the C-terminal carboxylic acid of the tryptophan residue in the B-chain is important for RXFP3 activity. In this study, we have added amide, alcohol, carbamate, and ester functionalities to the C-terminus of A2 and compared their structures and functions. As expected, the C-terminal amide form of A2 showed lower binding affinity for RXFP3 while ester and alcohol substitutions also demonstrated lower affinity. However, while these analogues showed slightly lower binding affinity, there was no significant difference in activation of RXFP3 compared to A2 bearing a C-terminal carboxylic acid, suggesting the binding pocket is able to accommodate additional atoms.

中文翻译：

C 端 B 链修饰对松弛素 3 激动剂类似物的影响

神经肽松弛素 3 的受体松弛素家族肽 3 (RXFP3) 受体是控制饮食、成瘾和精神行为的有吸引力的药理学靶点。对人松弛素 3（含有 3 个二硫键）及其类似物 A2（两个二硫键）的几项构效关系研究表明，B 链中色氨酸残基的 C 端羧酸对 RXFP3 活性很重要。在这项研究中，我们在 A2 的 C 端添加了酰胺、醇、氨基甲酸酯和酯官能团，并比较了它们的结构和功能。正如预期的那样，A2 的 C 端酰胺形式对 RXFP3 显示出较低的结合亲和力，而酯和醇取代也表现出较低的亲和力。然而，虽然这些类似物的结合亲和力略低，

更新日期：2020-11-12

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11