用于阿片样物质和胆囊收缩素（CCK）受体的酰肼连接双功能肽的部分反向、反向和顺向修饰
Partial retro-inverso, retro, and inverso modifications of hydrazide linked bifunctional peptides for opioid and cholecystokinin (CCK) receptors.
作者信息
Lee Yeon Sun, Agnes Richard S, Davis Peg, Ma Shou-wu, Badghisi Hamid, Lai Josephine, Porreca Frank, Hruby Victor J
机构信息
Department of Chemistry, University of Arizona, Tucson, Arizona 85721, USA.
出版信息
J Med Chem. 2007 Jan 11;50(1):165-8. doi: 10.1021/jm061268p.
Abstract
Partially modified retro-inverso, retro, and inverso isomers of hydrazide linked bifunctional peptides were designed, synthesized, and evaluated for bioactivities at delta/mu opioid receptors and CCK-1/CCK-2 receptors. All modifications of the CCK pharmacophore moiety affected bioactivities for the CCK-1 and CCK-2 receptors (up to 180-fold increase in the binding affinity with higher selectivity) and for the delta and mu opioid receptors. The results indicate that the opioid and CCK pharmacophores in one molecule interact with each other to induce topographical changes for both pharmacophores.
摘要
设计、合成并评估了酰肼连接双功能肽的部分修饰的反向异构体、反向异构体和顺反异构体在δ/μ阿片受体和CCK-1/CCK-2受体上的生物活性。CCK药效基团部分的所有修饰均影响CCK-1和CCK-2受体的生物活性（结合亲和力提高达180倍，选择性更高）以及δ和μ阿片受体的生物活性。结果表明，一个分子中的阿片类药物和CCK药效基团相互作用，导致两个药效基团的构象发生变化。
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本文引用的文献
1
Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors.基于阿片类和胆囊收缩素受体重叠药效基团的双功能肽的构效关系。
J Med Chem. 2006 May 18;49(10):2868-75. doi: 10.1021/jm050921q.
2
Design and synthesis of novel hydrazide-linked bifunctional peptides as delta/mu opioid receptor agonists and CCK-1/CCK-2 receptor antagonists.新型酰肼连接双功能肽作为δ/μ阿片受体激动剂和CCK-1/CCK-2受体拮抗剂的设计与合成
J Med Chem. 2006 Mar 9;49(5):1773-80. doi: 10.1021/jm050851n.
3
Neural basis for the hyperalgesic action of cholecystokinin in the rostral ventromedial medulla.胆囊收缩素在延髓头端腹内侧的痛觉过敏作用的神经基础。
J Neurophysiol. 2004 Oct;92(4):1982-9. doi: 10.1152/jn.00411.2004. Epub 2004 May 19.
4
Design of novel peptide ligands which have opioid agonist activity and CCK antagonist activity for the treatment of pain.设计具有阿片样物质激动剂活性和胆囊收缩素拮抗剂活性的新型肽配体用于治疗疼痛。
Life Sci. 2003 Jun 27;73(6):699-704. doi: 10.1016/s0024-3205(03)00390-4.
5
Cholecystokinin-B receptor antagonists attenuate morphine dependence and withdrawal in rats.胆囊收缩素B受体拮抗剂可减轻大鼠的吗啡依赖性和戒断反应。
Neuroreport. 2000 Mar 20;11(4):829-32. doi: 10.1097/00001756-200003200-00034.
6
Cholecystokinin/opioid interactions.胆囊收缩素/阿片类药物相互作用
Brain Res. 1999 Nov 27;848(1-2):78-89. doi: 10.1016/s0006-8993(99)01978-2.
7
CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology.
Prog Neurobiol. 1999 Jul;58(4):349-79. doi: 10.1016/s0301-0082(98)00090-2.
8
Tetrapeptide CCK agonists: structure-activity studies on modifications at the N-terminus.四肽缩胆囊素激动剂：N端修饰的构效关系研究
J Med Chem. 1994 Jan 21;37(2):309-13. doi: 10.1021/jm00028a015.
9
Potentiation of opiate analgesia and apparent reversal of morphine tolerance by proglumide.
Science. 1984 Apr 27;224(4647):395-6. doi: 10.1126/science.6546809.
10
Evidence for the neuropeptide cholecystokinin as an antagonist of opiate analgesia.神经肽缩胆囊素作为阿片类镇痛拮抗剂的证据。
Science. 1983 Jan 21;219(4582):310-2. doi: 10.1126/science.6294831.
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