具有二硫键的同时作为阿片受体激动剂和神经激肽-1 受体拮抗剂的肽类双功能化合物的生物活性和代谢稳定性。
The biological activity and metabolic stability of peptidic bifunctional compounds that are opioid receptor agonists and neurokinin-1 receptor antagonists with a cystine moiety.
机构信息
Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA.
出版信息
Bioorg Med Chem. 2009 Oct 15;17(20):7337-43. doi: 10.1016/j.bmc.2009.08.035. Epub 2009 Aug 21.
Abstract
In order to improve metabolic stability, a ring structure with a cystine moiety was introduced into TY027 (Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3',5'-(CF(3))(2)Bzl]), which is a lead compound of our developing bifunctional peptide possessing opioid agonist and NK1 antagonist activities. TY038 (Tyr-cyclo[D-Cys-Gly-Phe-Met-Pro-D-Cys]-Trp-NH-[3',5'-(CF(3))(2)Bzl]) was found as a highly selective delta opioid agonist over mu receptor in conventional tissue-based assays, together with an effective NK1 antagonist activity and good metabolic stability with more than 24h half life in rat plasma.
摘要
为了提高代谢稳定性，将一个带有胱氨酸部分的环结构引入到 TY027（Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3',5'-(CF(3))(2)Bzl]）中，这是我们正在开发的具有阿片样激动剂和 NK1 拮抗剂活性的双功能肽的先导化合物。TY038（Tyr-cyclo[D-Cys-Gly-Phe-Met-Pro-D-Cys]-Trp-NH-[3',5'-(CF(3))(2)Bzl]）在常规基于组织的测定中被发现是一种高度选择性的 delta 阿片样激动剂，对 mu 受体具有拮抗作用，同时具有有效的 NK1 拮抗剂活性和良好的代谢稳定性，在大鼠血浆中的半衰期超过 24 小时。
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