Dicarba analogues of the cyclic enkephalin peptides H-Tyr-c[D-Cys-Gly-Phe-D(or L)-Cys]NH2 retain high opioid activity
Dicarba analogues of the cyclic enkephalin peptides H-Tyr-c[D-Cys-Gly-Phe-D(or L)-Cys]NH2 retain high opioid activity
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DOI：
10.1021/jm061294n
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发表时间：
2007-03-22
影响因子：
7.3
通讯作者：
Schiller, Peter W.
中科院分区：
文献类型：
--
作者：
Berezowska, Irena;Chung, Nga N.;Schiller, Peter W.
通过用烯丙基甘氨酸取代半胱氨酸并在烯丙基甘氨酸残基侧链之间进行闭环复分解反应，在固相上合成了环阿片肽H-Tyr-c[D-Cys-Gly-Phe-D（或L）-Cys] NH 2的迪卡巴类似物。得到所得烯属肽的顺式和反式异构体的混合物，并且催化氢化产生饱和-CH 2-CH 2-桥接肽。迪卡巴类似物保留了高mu和δ激动剂效力。值得注意的是，H-Tyr-c[D-Allylgly-Gly-Phe-L-Allylgly] NH 2的反式异构体是对两种受体具有亚纳摩尔效力的μ激动剂/δ激动剂。
Dicarba analogues of the cyclic opioid peptides H-Tyr-c[D-Cys-Gly-Phe-D(or L)-Cys]NH2 were synthesized on solid phase by substituting allylglycines for the cysteines and cyclization by ring-closing metathesis between the side chains of the allylglycine residues. Mixtures of cis and trans isomers of the resulting olefinic peptides were obtained, and catalytic hydrogenation yielded the saturated -CH2-CH2- bridged peptides. The dicarba analogues retained high mu and delta agonist potencies. Remarkably, the trans isomer of H-Tyr-c[D-Allylgly-Gly-Phe-L-Allylgly]NH2 was a mu agonist/delta agonist with subnanomolar potency at both receptors.