A novel N-terminal cyclic dynorphin a analogue cycloN,5[Trp3,Trp4,Glu5] dynorphin A-(1-11)NH2 that lacks the basic N-terminus

被引：29

作者：

Vig, BS

Murray, TF

Aldrich, JV ^{[1
]}

机构：

[1] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA

[2] Univ Georgia, Coll Vet Med, Dept Physiol & Pharmacol, Athens, GA 30602 USA

[3] Univ Kansas, Sch Pharm, Dept Med Chem, Lawrence, KS 66045 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 08期

关键词：

D O I：

10.1021/jm0256023

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel N-terminal-to-side chain cyclic dynorphin A analogue lacking the basic N-terminus was designed based on Ac[LyS(2),Trp(3),Trp(4),D-Ala(8)]dynorphin A-(1-11)NH2 (Wan et al. J. Med. Chem. 1999, 42, 3011-3013). cyclo(N-5)-[Trp(3),Trp(4),Glu(5)]dynorphin A-(1-11)NH2 showed similar kappa opioid receptor affinity (K-i = 27 nM) and selectivity (K-i ratio (kappa/mu/delta) = 1/12/330) to the linear peptide and antagonized dynorphin A-(1 - 13)NH2 at kappa opioid receptors. This is the first opioid peptide cyclized through the N-terminus that retains high opioid receptor affinity.

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页码：1279 / 1282

页数：4

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