Constraining Endomorphin-1 by β,α-Hybrid Dipeptide/Heterocycle Scaffolds: Identification of a Novel k-Opioid Receptor Selective Partial Agonist

被引：20

作者：

De Marco, Rossella ^{[1
]}

Bedini, Andrea ^{[2
]}

Spampinato, Santi ^{[2
]}

Comellini, Lorenzo ^{[1
]}

Zhao, Junwei ^{[1
]}

Artali, Roberto ^{[3
]}

Gentilucci, Luca ^{[1
]}

机构：

[1] Univ Bologna, Dept Chem G Ciamician, Via Selmi 2, I-40126 Bologna, Italy

[2] Univ Bologna, Dept Pharm & Biotechnol, Via Irnerio 48, I-40126 Bologna, Italy

[3] Scientia Advice, I-20832 Monza, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 61卷 / 13期

关键词：

ENZYMATIC-HYDROLYSIS; PROLINE SURROGATES; ANALOGS; PEPTIDE; POTENT; LIGANDS; STABILITY; AFFINITY; DESIGN; SYSTEM;

D O I：

10.1021/acs.jmedchem.8b00296

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein we present the expedient synthesis of endomorphin-1 analogues containing stereoisomeric beta(2)-homo-Freidinger lactam-like scaffolds ([Amo(2)]EM), and we discuss opioid receptor (OR) affinity, enzymatic stability, functional activity, in vivo antinociceptive effects, and conformational and molecular docking analysis. Hence, H-Tyr-Amo-Trp-PheNH(2) resulted to be a new chemotype of highly stable, selective, partial KOR agonist inducing analgesia, therefore displaying great potential interest as a painkiller possibly with reduced harmful side effects.

引用

页码：5751 / 5757

页数：7

共 46 条

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