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CoMFA-based comparison of two models of binding site on adenosine A1 receptor

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Abstract

A set of 32 N6-substituted adenosines and 22 8-substituted xanthines with affinity for adenosine A1 receptors was subjected to three-dimensional quantitative structure-affinity relationship analysis using comparative molecular field analysis (CoMFA). The aim was to compare two modes of binding to the receptor – `N6-C8' and `N6-N7'. Good models with high predictive power and stability were obtained. A comparison of these models gives the following results: (a) Inclusion of both steric and electrostatic fields in CoMFA generates better predictive models compared to models based on steric or electrostatic fields alone. (b) The `N6-N7' CoMFA models are slightly better than the `N6-C8' ones. (c) Steric restriction exists around the N6-H in the `N6-N7' steric field map, which is absent in the `N6-C8' steric field map. This report demonstrates that the `N6-N7' mode of binding is a further development of the `N6-C8' model with a slightly better predictive ability and more accurate steric and electrostatic overlaps between agonists and antagonists.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Pharmacy, Medical University Sofia, 1000, Sofia, Bulgaria

    Irini Doytchinova

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  1. Irini Doytchinova
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Doytchinova, I. CoMFA-based comparison of two models of binding site on adenosine A1 receptor. J Comput Aided Mol Des 15, 29–39 (2001). https://doi.org/10.1023/A:1011150120831

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