TY - JOUR
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.
UR - https://www.scopus.com/pages/publications/0001676081
UR - https://www.scopus.com/inward/citedby.url?scp=0001676081&partnerID=8YFLogxK
U2 - 10.1073/pnas.82.1.236
DO - 10.1073/pnas.82.1.236
M3 - Article
C2 - 2857488
AN - SCOPUS:0001676081
SN - 0027-8424
VL - 82
SP - 236
EP - 239
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
IS - 1
ER -