具有高μ-阿片受体特异性的生长抑素构象受限类似物。
Conformationally restricted analogs of somatostatin with high mu-opiate receptor specificity.
作者信息
Pelton J T, Gulya K, Hruby V J, Duckles S P, Yamamura H I
出版信息
Proc Natl Acad Sci U S A. 1985 Jan;82(1):236-9. doi: 10.1073/pnas.82.1.236.
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 mu-opiate receptors (IC50 value of [3H]naloxone = 3.5 nM), being 7800 times more potent than somatostatin. The cyclic octapeptide also displayed high mu-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 mu-opiate receptors may be of use in examining the physiological role(s) of the mu-opiate receptor.
摘要
已经制备了一系列生长抑素的环状、构象受限类似物，并测试了它们抑制[3H]纳洛酮和[D - Ala2, D - Leu5][3H]脑啡肽与大鼠脑膜结合的能力。最有效的类似物是D - Phe - Cys - Tyr - D - Trp - Lys - Thr - Pen - Thr - NH2，其中Pen是[D - Phe5, Cys6, Tyr7, D - Trp8, Pen11]生长抑素-(5 - 12)-八肽酰胺中的青霉胺，它对μ - 阿片受体具有高亲和力（[3H]纳洛酮的IC50值 = 3.5 nM），比生长抑素强7800倍。该环八肽还表现出高μ - 阿片受体选择性，IC50[(D - Ala2,D - Leu5]脑啡肽)/IC50（纳洛酮）的比值为271。生长抑素类似物对μ - 阿片受体的高亲和力和选择性可能有助于研究μ - 阿片受体的生理作用。
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1
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Life Sci. 1982 Jun 21;30(25):2191-202. doi: 10.1016/0024-3205(82)90293-4.
2
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Science. 1981 Apr 3;212(4490):75-7. doi: 10.1126/science.6259732.
3
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J Biol Chem. 1983 May 10;258(9):5525-30.
4
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5
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6
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9
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