Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors

K. Gulya, John T. Pelton, Victor J. Hruby, Henry I. Yamamura

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

A series of cyclic conformationally restricted penicillamine containing somatostatin octapeptide analogues have been prepared by standard solid phase synthetic techniques and tested for their ability to inhibit specific [125I]CGP 23,996 (des-Ala1-,Gly2-[desamino-Cys3Tyr11]-dicarba3,14- somatostatin), [3H]naloxone or [3H]DPDPE ([D-Pen2-D-Pen5]enkephalin) binding in rat brain membrane preparations. We now report structure-activity relationship studies with the syntheis of our most potent and selective mu opioid receptor compound DPheCysTyrDTrpOrnThrPenThrNH2, which we refer to as Cys2Tyr3Orn5Pen7-amide. While this octapeptide exhibited high affinity (IC50 = 2.80 nM) for an apparently single population of binding sites (nH = 0.89 ± 0.1) and exceptional selectivity for mu opioid receptos with an IC51(DPDPE)/IC50 (naloxone) ratio of 4,829, it also displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM). Thus, Cys2Tyr3Orn5 Pen7-amide may be the ligand of choice for further characterization of mu opioid receptors and for examining the physiological role of this class of receptors.

Original languageEnglish
Pages (from-to)2221-2229
Number of pages9
JournalLife Sciences
Volume38
Issue number24
DOIs
Publication statusPublished - Jun 16 1986

Fingerprint

D-Penicillamine (2,5)-Enkephalin
mu Opioid Receptor
Somatostatin
Inhibitory Concentration 50
Naloxone
Amides
Somatostatin Receptors
Penicillamine
Structure-Activity Relationship
Opioid Analgesics
Rats
Brain
Binding Sites
Ligands
Membranes
Population

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors. / Gulya, K.; Pelton, John T.; Hruby, Victor J.; Yamamura, Henry I.

In: Life Sciences, Vol. 38, No. 24, 16.06.1986, p. 2221-2229.

Research output: Contribution to journalArticle

Gulya, K. ; Pelton, John T. ; Hruby, Victor J. ; Yamamura, Henry I. / Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors. In: Life Sciences. 1986 ; Vol. 38, No. 24. pp. 2221-2229.
@article{e666652a638944bd9959692f23e1a2f8,
title = "Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors",
abstract = "A series of cyclic conformationally restricted penicillamine containing somatostatin octapeptide analogues have been prepared by standard solid phase synthetic techniques and tested for their ability to inhibit specific [125I]CGP 23,996 (des-Ala1-,Gly2-[desamino-Cys3Tyr11]-dicarba3,14- somatostatin), [3H]naloxone or [3H]DPDPE ([D-Pen2-D-Pen5]enkephalin) binding in rat brain membrane preparations. We now report structure-activity relationship studies with the syntheis of our most potent and selective mu opioid receptor compound DPheCysTyrDTrpOrnThrPenThrNH2, which we refer to as Cys2Tyr3Orn5Pen7-amide. While this octapeptide exhibited high affinity (IC50 = 2.80 nM) for an apparently single population of binding sites (nH = 0.89 ± 0.1) and exceptional selectivity for mu opioid receptos with an IC51(DPDPE)/IC50 (naloxone) ratio of 4,829, it also displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM). Thus, Cys2Tyr3Orn5 Pen7-amide may be the ligand of choice for further characterization of mu opioid receptors and for examining the physiological role of this class of receptors.",
author = "K. Gulya and Pelton, {John T.} and Hruby, {Victor J.} and Yamamura, {Henry I.}",
year = "1986",
month = "6",
day = "16",
doi = "10.1016/0024-3205(86)90574-6",
language = "English",
volume = "38",
pages = "2221--2229",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "24",

}

TY - JOUR

T1 - Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors

AU - Gulya, K.

AU - Pelton, John T.

AU - Hruby, Victor J.

AU - Yamamura, Henry I.

PY - 1986/6/16

Y1 - 1986/6/16

N2 - A series of cyclic conformationally restricted penicillamine containing somatostatin octapeptide analogues have been prepared by standard solid phase synthetic techniques and tested for their ability to inhibit specific [125I]CGP 23,996 (des-Ala1-,Gly2-[desamino-Cys3Tyr11]-dicarba3,14- somatostatin), [3H]naloxone or [3H]DPDPE ([D-Pen2-D-Pen5]enkephalin) binding in rat brain membrane preparations. We now report structure-activity relationship studies with the syntheis of our most potent and selective mu opioid receptor compound DPheCysTyrDTrpOrnThrPenThrNH2, which we refer to as Cys2Tyr3Orn5Pen7-amide. While this octapeptide exhibited high affinity (IC50 = 2.80 nM) for an apparently single population of binding sites (nH = 0.89 ± 0.1) and exceptional selectivity for mu opioid receptos with an IC51(DPDPE)/IC50 (naloxone) ratio of 4,829, it also displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM). Thus, Cys2Tyr3Orn5 Pen7-amide may be the ligand of choice for further characterization of mu opioid receptors and for examining the physiological role of this class of receptors.

AB - A series of cyclic conformationally restricted penicillamine containing somatostatin octapeptide analogues have been prepared by standard solid phase synthetic techniques and tested for their ability to inhibit specific [125I]CGP 23,996 (des-Ala1-,Gly2-[desamino-Cys3Tyr11]-dicarba3,14- somatostatin), [3H]naloxone or [3H]DPDPE ([D-Pen2-D-Pen5]enkephalin) binding in rat brain membrane preparations. We now report structure-activity relationship studies with the syntheis of our most potent and selective mu opioid receptor compound DPheCysTyrDTrpOrnThrPenThrNH2, which we refer to as Cys2Tyr3Orn5Pen7-amide. While this octapeptide exhibited high affinity (IC50 = 2.80 nM) for an apparently single population of binding sites (nH = 0.89 ± 0.1) and exceptional selectivity for mu opioid receptos with an IC51(DPDPE)/IC50 (naloxone) ratio of 4,829, it also displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM). Thus, Cys2Tyr3Orn5 Pen7-amide may be the ligand of choice for further characterization of mu opioid receptors and for examining the physiological role of this class of receptors.

UR - http://www.scopus.com/inward/record.url?scp=0022469482&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022469482&partnerID=8YFLogxK

U2 - 10.1016/0024-3205(86)90574-6

DO - 10.1016/0024-3205(86)90574-6

M3 - Article

C2 - 2872570

AN - SCOPUS:0022469482

VL - 38

SP - 2221

EP - 2229

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 24

ER -