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新型神经降压素模拟物的合理设计：发现一种药理学上前所未有的药物，其表现出浓度依赖性的双重作用，既是拮抗剂又是完全激动剂。

Rational design of novel neurotensin mimetics: discovery of a pharmacologically unprecedented agent exhibiting concentration-dependent dual effects as antagonist and full agonist.

作者信息

Pang Y P, Zaidi J, Kozikowski A P, Cusack B, Richelson E

机构信息

Mayo Foundation for Medical Education and Research, Jacksonville, FL 32224.

出版信息

J Comput Aided Mol Des. 1994 Aug;8(4):433-40. doi: 10.1007/BF00125377.

DOI:10.1007/BF00125377
PMID:7815094
Abstract

We report the rational design of novel neurotensin mimetics through use of the Multiple Template Approach. This approach is based on our notion that a flexible peptide can be replaced by a partially flexible molecule, identified through testing a comparatively small number of molecules possessing a different intrinsic availability of conformations of the native peptide. The Multiple Template Approach has culminated in the discovery of a pharmacologically unprecedented agent, which behaves as a neurotensin antagonist at low concentration and as a full neurotensin agonist at high concentration.

摘要

我们报告了通过使用多重模板方法对新型神经降压素模拟物进行的合理设计。这种方法基于我们的观念，即一个柔性肽可以被一个部分柔性的分子所取代，该分子是通过测试相对少量具有天然肽不同内在构象可用性的分子而确定的。多重模板方法最终发现了一种药理学上前所未有的药物，它在低浓度时表现为神经降压素拮抗剂，而在高浓度时表现为完全的神经降压素激动剂。

相似文献

1
Rational design of novel neurotensin mimetics: discovery of a pharmacologically unprecedented agent exhibiting concentration-dependent dual effects as antagonist and full agonist.新型神经降压素模拟物的合理设计：发现一种药理学上前所未有的药物，其表现出浓度依赖性的双重作用，既是拮抗剂又是完全激动剂。
J Comput Aided Mol Des. 1994 Aug;8(4):433-40. doi: 10.1007/BF00125377.
2
Pharmacological studies on novel neurotensin mimetics: discovery of a pharmacologically unique agent exhibiting concentration-dependent dual effects as antagonist and agonist.新型神经降压素模拟物的药理学研究：发现一种具有药理学独特性的药物，其表现出浓度依赖性的双重作用，兼具拮抗剂和激动剂活性。
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本文引用的文献

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Neurotensin modulates dopamine neurotransmission at several levels along brain dopaminergic pathways.神经降压素在大脑多巴胺能通路的多个水平调节多巴胺神经传递。
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Desensitization and down-regulation of neurotensin receptors in murine neuroblastoma clone N1E-115 by [D-Lys8] neurotensin(8-13).
[D-赖氨酸8]神经降压素（8-13）对小鼠神经母细胞瘤克隆N1E-115中神经降压素受体的脱敏和下调作用
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Pharmacological studies on novel neurotensin mimetics: discovery of a pharmacologically unique agent exhibiting concentration-dependent dual effects as antagonist and agonist.新型神经降压素模拟物的药理学研究：发现一种具有药理学独特性的药物，其表现出浓度依赖性的双重作用，兼具拮抗剂和激动剂活性。
Mol Pharmacol. 1993 Nov;44(5):1036-40.
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Possible conformations involved in the binding of neurotensin, xenopsin and bradykinin molecules to mast cell receptors.神经降压素、异视紫质和缓激肽分子与肥大细胞受体结合时可能涉及的构象。
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Functional group contributions to drug-receptor interactions.
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