Conformationally restricted analogs of somatostatin with high μ-opiate receptor specificity

J. T. Pelton; K. Gulya; V. J. Hruby; S. P. Duckles; H. I. Yamamura

doi:10.1073/pnas.82.1.236

Conformationally restricted analogs of somatostatin with high μ-opiate receptor specificity

J. T. Pelton
, K. Gulya
, V. J. Hruby
, S. P. Duckles
, H. I. Yamamura

Research output: Contribution to journal › Article › peer-review

111 Scopus citations

Abstract

A series of cyclic, conformationally restricted analogs of somatostatin have been prepared and tested for their ability to inhibit the binding of [³H]naloxone and [D-Ala², D-Leu⁵][³H]enkephalin to rat brain membranes. The most potent analog, D-Phe[Cys-Tyr-D-Trp-Lys-Thr-Pen]-Thr-NH₂ where Pen is penicillamine in [D-Phe⁵,[Cys⁶, Tyr⁷, D-Trp⁸, Pen¹¹]]somatostatin-(5-12)-octapeptide amide, exhibited high affinity for μ-opiate receptors (IC₅₀ value of [³H]naloxone = 3.5 nM), being 7800 times more potent than somatostatin. The cyclic octapeptide also displayed high μ-opiate receptor selectivity with an IC₅₀ ([D-Ala²-, D-Leu⁵]enkephalin)/IC₅₀ (naloxone) ratio of 271. The high affinity and selectivity of the somatostatin analog for μ-opiate receptors may be of use in examining the physiological role(s) of the μ-opiate receptor.

Original language	English (US)
Pages (from-to)	236-239
Number of pages	4
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	82
Issue number	1
DOIs	https://doi.org/10.1073/pnas.82.1.236
State	Published - 1985
Externally published	Yes

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title = "Conformationally restricted analogs of somatostatin with high μ-opiate receptor specificity",

abstract = "A series of cyclic, conformationally restricted analogs of somatostatin have been prepared and tested for their ability to inhibit the binding of [3H]naloxone and [D-Ala2, D-Leu5][3H]enkephalin to rat brain membranes. The most potent analog, D-Phe[Cys-Tyr-D-Trp-Lys-Thr-Pen]-Thr-NH2 where Pen is penicillamine in [D-Phe5,[Cys6, Tyr7, D-Trp8, Pen11]]somatostatin-(5-12)-octapeptide amide, exhibited high affinity for μ-opiate receptors (IC50 value of [3H]naloxone = 3.5 nM), being 7800 times more potent than somatostatin. The cyclic octapeptide also displayed high μ-opiate receptor selectivity with an IC50 ([D-Ala2-, D-Leu5]enkephalin)/IC50 (naloxone) ratio of 271. The high affinity and selectivity of the somatostatin analog for μ-opiate receptors may be of use in examining the physiological role(s) of the μ-opiate receptor.",

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year = "1985",

doi = "10.1073/pnas.82.1.236",

language = "English (US)",

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T1 - Conformationally restricted analogs of somatostatin with high μ-opiate receptor specificity

AU - Pelton, J. T.

AU - Gulya, K.

AU - Hruby, V. J.

AU - Duckles, S. P.

AU - Yamamura, H. I.

PY - 1985

Y1 - 1985

N2 - A series of cyclic, conformationally restricted analogs of somatostatin have been prepared and tested for their ability to inhibit the binding of [3H]naloxone and [D-Ala2, D-Leu5][3H]enkephalin to rat brain membranes. The most potent analog, D-Phe[Cys-Tyr-D-Trp-Lys-Thr-Pen]-Thr-NH2 where Pen is penicillamine in [D-Phe5,[Cys6, Tyr7, D-Trp8, Pen11]]somatostatin-(5-12)-octapeptide amide, exhibited high affinity for μ-opiate receptors (IC50 value of [3H]naloxone = 3.5 nM), being 7800 times more potent than somatostatin. The cyclic octapeptide also displayed high μ-opiate receptor selectivity with an IC50 ([D-Ala2-, D-Leu5]enkephalin)/IC50 (naloxone) ratio of 271. The high affinity and selectivity of the somatostatin analog for μ-opiate receptors may be of use in examining the physiological role(s) of the μ-opiate receptor.

AB - A series of cyclic, conformationally restricted analogs of somatostatin have been prepared and tested for their ability to inhibit the binding of [3H]naloxone and [D-Ala2, D-Leu5][3H]enkephalin to rat brain membranes. The most potent analog, D-Phe[Cys-Tyr-D-Trp-Lys-Thr-Pen]-Thr-NH2 where Pen is penicillamine in [D-Phe5,[Cys6, Tyr7, D-Trp8, Pen11]]somatostatin-(5-12)-octapeptide amide, exhibited high affinity for μ-opiate receptors (IC50 value of [3H]naloxone = 3.5 nM), being 7800 times more potent than somatostatin. The cyclic octapeptide also displayed high μ-opiate receptor selectivity with an IC50 ([D-Ala2-, D-Leu5]enkephalin)/IC50 (naloxone) ratio of 271. The high affinity and selectivity of the somatostatin analog for μ-opiate receptors may be of use in examining the physiological role(s) of the μ-opiate receptor.

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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ER -

Conformationally restricted analogs of somatostatin with high μ-opiate receptor specificity

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