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用于阿片样物质和胆囊收缩素（CCK）受体的酰肼连接双功能肽的部分反向、反向和顺向修饰

Partial retro-inverso, retro, and inverso modifications of hydrazide linked bifunctional peptides for opioid and cholecystokinin (CCK) receptors.

作者信息

Lee Yeon Sun, Agnes Richard S, Davis Peg, Ma Shou-wu, Badghisi Hamid, Lai Josephine, Porreca Frank, Hruby Victor J

机构信息

Department of Chemistry, University of Arizona, Tucson, Arizona 85721, USA.

出版信息

J Med Chem. 2007 Jan 11;50(1):165-8. doi: 10.1021/jm061268p.

DOI:10.1021/jm061268p
PMID:17201419
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2365893/
Abstract

Partially modified retro-inverso, retro, and inverso isomers of hydrazide linked bifunctional peptides were designed, synthesized, and evaluated for bioactivities at delta/mu opioid receptors and CCK-1/CCK-2 receptors. All modifications of the CCK pharmacophore moiety affected bioactivities for the CCK-1 and CCK-2 receptors (up to 180-fold increase in the binding affinity with higher selectivity) and for the delta and mu opioid receptors. The results indicate that the opioid and CCK pharmacophores in one molecule interact with each other to induce topographical changes for both pharmacophores.

摘要

设计、合成并评估了酰肼连接双功能肽的部分修饰的反向异构体、反向异构体和顺反异构体在δ/μ阿片受体和CCK-1/CCK-2受体上的生物活性。CCK药效基团部分的所有修饰均影响CCK-1和CCK-2受体的生物活性（结合亲和力提高达180倍，选择性更高）以及δ和μ阿片受体的生物活性。结果表明，一个分子中的阿片类药物和CCK药效基团相互作用，导致两个药效基团的构象发生变化。

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Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors.基于阿片类和胆囊收缩素受体重叠药效基团的双功能肽的构效关系。
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Design and synthesis of novel hydrazide-linked bifunctional peptides as delta/mu opioid receptor agonists and CCK-1/CCK-2 receptor antagonists.新型酰肼连接双功能肽作为δ/μ阿片受体激动剂和CCK-1/CCK-2受体拮抗剂的设计与合成
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