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源自还原型聚酰胺的二氮杂环肽模拟化合物的阿片样物质亲和力

Opioid Affinity of Diazacyclic Peptidomimetic Compounds Derived from Reduced Polyamides.

作者信息

Chaudhari Prakash, Bunnell Ashley, Yegambaram Manivannan, Dooley Colette, Nefzi Adel

机构信息

Department of Cellular Biology & Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Center for Translational Science, Port Saint Lucie, FL 34987, USA.

Independent Researcher, Vero Beach, FL 32960, USA.

出版信息

Int J Mol Sci. 2025 Aug 25;26(17):8249. doi: 10.3390/ijms26178249.

DOI:10.3390/ijms26178249
PMID:40943174
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12428765/
Abstract

Diaza-peptidomimetics are constrained compounds that mimic the biological efficacy of peptides while offering increased stability. We have previously reported the synthesis of bis-cyclic guanidine heterocyclic peptidomimetics as opioid ligands with mixed μ-, κ- and δ-opioid receptor interactions and their potential activity as novel analgesics. Using the same approach, we report here the synthesis of sulfonated and piperazine-tethered bis-cyclic guanidines and their in vitro screening results from radioligand competition binding assays at the μ- (MOR), δ- (DOR), and κ- (KOR) opioid receptors.

摘要

二氮杂肽模拟物是一类受限化合物，它们在具有更高稳定性的同时能够模拟肽的生物学功效。我们之前曾报道过双环胍杂环肽模拟物的合成，这类化合物作为阿片样物质配体，与μ-、κ-和δ-阿片受体具有混合相互作用，并且具有作为新型镇痛药的潜在活性。采用相同的方法，我们在此报告磺化和哌嗪连接的双环胍的合成，以及它们在μ-（MOR）、δ-（DOR）和κ-（KOR）阿片受体上进行放射性配体竞争结合试验的体外筛选结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/545b/12428765/1690432604ef/ijms-26-08249-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/545b/12428765/daefb202298e/ijms-26-08249-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/545b/12428765/1690432604ef/ijms-26-08249-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/545b/12428765/daefb202298e/ijms-26-08249-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/545b/12428765/1690432604ef/ijms-26-08249-sch001.jpg

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Synthesis of Diazacyclic and Triazacyclic Small-Molecule Libraries Using Vicinal Chiral Diamines Generated from Modified Short Peptides and Their Application for Drug Discovery.利用修饰短肽产生的邻位手性二胺合成二氮杂环和三氮杂环小分子文库及其在药物发现中的应用。
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