• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>other >Development of Cyclic γ-MSH Analogues with Selective hMC3R Agonist and hMC3R/hMC5R Antagonist Activities
【2h】

Development of Cyclic γ-MSH Analogues with Selective hMC3R Agonist and hMC3R/hMC5R Antagonist Activities

机译：具有选择性hMC3R激动剂和hMC3R / hMC5R拮抗活性的环状γ-MSH类似物的开发

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A series of cyclic lactam analogues of γ-MSH (H-Tyr1-Val2-Met3-Gly4-His5-Phe6-Arg7-Trp8-Asp9-Arg10-Phe11-Gly12-OH) with a bulky hydrophobic residue in the direct proximity to the pharmacophore (Xaa-d-Phe/d-Nal(2′)-Arg-Trp) were designed and synthesized by solid-phase methods. A variety of amino acids with a broad range of hydrophobic/hydrophilic properties was introduced in position 5 to further explore their complementary role in receptor selectivity. Biological evaluation of these peptides revealed several analogues with potent hMC3R agonist and hMC3R/hMC5R antagonist activities, and good receptor selectivity. Analogue >4, c[Nle-Arg-d-Phe-Arg-Trp-Glu]-NH2, was found to be a very potent and selective hMC3R agonist (EC50 = 1.2 nM, 112% act). In addition, analogue >13, c[Nle-Val-d-Nal(2′)-Arg-Trp-Glu]-NH2, was identified as an hMC3R/hMC5R antagonist with the best selectivity against the hMC4R in this series (pA2(hMC3R) = 8.4; pA2(hMC5R) = 8.7). These results indicate the significance of steric factors in melanocortin receptor selectivity and suggest that introduction of bulky residues in the direct proximity to the melanocortin pharmacophore is an effective approach to design of novel hMC3R and hMC5R selective ligands.
机译：γ-MSH的一系列环状内酰胺类似物（H-Tyr 1 -Val 2 -Met 3 -Gly 4 -His 5 -Phe 6 -Arg 7 -Trp 8 -Asp 9 -Arg 10 -Phe 11 -Gly 12 -OH），在药效团（Xaa-通过固相方法设计合成了d-Phe / d-Nal（2'）-Arg-Trp）。在位置5引入了具有广泛疏水性/亲水性的各种氨基酸，以进一步探索其在受体选择性中的互补作用。这些肽的生物学评估显示了具有强大的hMC3R激动剂和hMC3R / hMC5R拮抗剂活性以及良好的受体选择性的几种类似物。发现类似物> 4 ：c [Nle-Arg-d-Phe-Arg-Trp-Glu] -NH2是非常有效的选择性hMC3R激动剂（EC50 = 1.2 nM，112％作用） 。此外，类似物> 13 ，即c [Nle-Val-d-Nal（2'）-Arg-Trp-Glu] -NH2被确定为hMC3R / hMC5R拮抗剂，对该化合物的选择性最高此系列中的hMC4R（pA2（hMC3R）= 8.4； pA2（hMC5R）= 8.7）。这些结果表明空间因素在黑皮质素受体选择性中的重要性，并表明在黑皮质素药效基团的直接附近引入大的残基是设计新型hMC3R和hMC5R选择性配体的有效方法。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号