A new nicotinic acetylcholine minireceptor model:: a theoretical thermodynamic analysis of simultaneous cation-π and hydrogen bond interactions

被引：10

作者：

Barreiro, EJ

Barreiro, G

Guimaraes, CRW

de Alencastro, RB

机构：

[1] UFRJ, Fac Farm, Dept Farm, Lab Avaliacao & Sintese Substancias Bioativas, BR-21949910 Rio De Janeiro, Brazil

[2] UFRJ, Dept Quim Organ, Phys Organ Chem Grp, Inst Quim, BR-21949900 Rio De Janeiro, Brazil

来源：

JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM | 2000年 / 532卷

关键词：

cation-pi and hydrogen bond interactions; ligand-minireceptor complexes; nicotinic acetylcholine receptor (nAChR) model;

D O I：

10.1016/S0166-1280(00)00508-X

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

In this work, we developed a nicotinic acetylcholine receptor (nAChR) model using the minireceptor modeling technique. For the construction of the minireceptor model, we elected some known nicotinic agonists according to their structural characteristics and binding constants (Ki) values, The results show an orientation pattern for the probes' distances and angles in the model, These data suggest that the strategy used to build the minireceptor is able to reproduce geometrically the cation-pi and hydrogen bond interactions between ligands and the nAChR, In order to obtain an energetic validation for the minireceptor, we derived a quantitative model of interaction that includes the desolvation step of the ligands for all ligand-minireceptor complexes. We observed a good agreement between the experimental and the calculated free-energy of complexation. This new nAChR minireceptor model can be employed in the molecular design of new nicotinic agonist candidates that may represent new lead-compounds for the treatment of cognitive disorders. (C) 2000 Elsevier Science B.V. All rights reserved.

引用

页码：11 / 22

页数：12

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