Cyclic enkephalin analogues with exceptional potency and selectivity for δ-opioid receptors

Victor J. Hruby; Hubert Bartosz-Bechowski; Peg Davis; Jirina Slaninova; Teresa Zalewska; Dagmar Stropova; Frank Porreca; Henry I. Yamamura

doi:10.1021/jm9704762

Cyclic enkephalin analogues with exceptional potency and selectivity for δ-opioid receptors

Victor J. Hruby, Hubert Bartosz-Bechowski, Peg Davis, Jirina Slaninova, Teresa Zalewska, Dagmar Stropova, Frank Porreca, Henry I. Yamamura

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Abstract

Superpotent and highly δ-opioid receptor selective cyclic peptides of the general formula H-Tyr-c[D-Pen-Gly-Phe(p-X)-Pen]-Phe-OH (where X = hydrogen or halogen) have been synthesized. In the binding assays the most selective and most potent compound is the p-bromophenyl-alanine-4 analogue (IC₅₀ value = 0.19 nM, selectivity ratio = 21 000 for δ vs μ). In the GPI and MVD bioassays the most selective and most potent analogue is the p- fluoro-substituted analogue Tyr-[D-Pen-Gly-Phe(p-F)-Pen]-Phe-OH. In the MVD assay it has an exceptionally low IC₅₀ value of 0.016 nM and a δ vs μ selectivity ratio of 45 000.

Original language	English (US)
Pages (from-to)	3957-3962
Number of pages	6
Journal	Journal of Medicinal Chemistry
Volume	40
Issue number	24
DOIs	https://doi.org/10.1021/jm9704762
State	Published - 1997

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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title = "Cyclic enkephalin analogues with exceptional potency and selectivity for δ-opioid receptors",

abstract = "Superpotent and highly δ-opioid receptor selective cyclic peptides of the general formula H-Tyr-c[D-Pen-Gly-Phe(p-X)-Pen]-Phe-OH (where X = hydrogen or halogen) have been synthesized. In the binding assays the most selective and most potent compound is the p-bromophenyl-alanine-4 analogue (IC50 value = 0.19 nM, selectivity ratio = 21 000 for δ vs μ). In the GPI and MVD bioassays the most selective and most potent analogue is the p- fluoro-substituted analogue Tyr-[D-Pen-Gly-Phe(p-F)-Pen]-Phe-OH. In the MVD assay it has an exceptionally low IC50 value of 0.016 nM and a δ vs μ selectivity ratio of 45 000.",

author = "Hruby, {Victor J.} and Hubert Bartosz-Bechowski and Peg Davis and Jirina Slaninova and Teresa Zalewska and Dagmar Stropova and Frank Porreca and Yamamura, {Henry I.}",

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doi = "10.1021/jm9704762",

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T1 - Cyclic enkephalin analogues with exceptional potency and selectivity for δ-opioid receptors

AU - Hruby, Victor J.

AU - Bartosz-Bechowski, Hubert

AU - Davis, Peg

AU - Slaninova, Jirina

AU - Zalewska, Teresa

AU - Stropova, Dagmar

AU - Porreca, Frank

AU - Yamamura, Henry I.

PY - 1997

Y1 - 1997

N2 - Superpotent and highly δ-opioid receptor selective cyclic peptides of the general formula H-Tyr-c[D-Pen-Gly-Phe(p-X)-Pen]-Phe-OH (where X = hydrogen or halogen) have been synthesized. In the binding assays the most selective and most potent compound is the p-bromophenyl-alanine-4 analogue (IC50 value = 0.19 nM, selectivity ratio = 21 000 for δ vs μ). In the GPI and MVD bioassays the most selective and most potent analogue is the p- fluoro-substituted analogue Tyr-[D-Pen-Gly-Phe(p-F)-Pen]-Phe-OH. In the MVD assay it has an exceptionally low IC50 value of 0.016 nM and a δ vs μ selectivity ratio of 45 000.

AB - Superpotent and highly δ-opioid receptor selective cyclic peptides of the general formula H-Tyr-c[D-Pen-Gly-Phe(p-X)-Pen]-Phe-OH (where X = hydrogen or halogen) have been synthesized. In the binding assays the most selective and most potent compound is the p-bromophenyl-alanine-4 analogue (IC50 value = 0.19 nM, selectivity ratio = 21 000 for δ vs μ). In the GPI and MVD bioassays the most selective and most potent analogue is the p- fluoro-substituted analogue Tyr-[D-Pen-Gly-Phe(p-F)-Pen]-Phe-OH. In the MVD assay it has an exceptionally low IC50 value of 0.016 nM and a δ vs μ selectivity ratio of 45 000.

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Cyclic enkephalin analogues with exceptional potency and selectivity for δ-opioid receptors

Abstract

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