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. 2007 Mar 22;50(6):1414-7.
doi: 10.1021/jm061294n. Epub 2007 Feb 22.

Dicarba analogues of the cyclic enkephalin peptides H-Tyr-c[D-Cys-Gly-Phe-D(or L)-Cys]NH(2) retain high opioid activity

Irena Berezowska  1 , Nga N Chung, Carole Lemieux, Brian C Wilkes, Peter W Schiller
Affiliations

Dicarba analogues of the cyclic enkephalin peptides H-Tyr-c[D-Cys-Gly-Phe-D(or L)-Cys]NH(2) retain high opioid activity

Irena Berezowska et al. J Med Chem. .

Abstract

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.

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Figures

Figure 1
Figure 1
Dicarba analogues of H-Tyr-c[D-Cys-Gly-Phe-D(or L)Cys]NH2
Figure 2
Figure 2
Low-energy conformers of compounds 1–4 corresponding to the model of the δ receptor-bound conformation.
See this image and copyright information in PMC

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