IMR Press / FBL / Volume 7 / Issue 4 / DOI: 10.2741/A876

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Quantitative relationships between ryanoids, receptor affinity and channel conductance
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1 Department of Biochemistry/330, University of Nevada, Reno, Nevada, USA
Academic Editor:Hector Valdivia
Front. Biosci. (Landmark Ed) 2002, 7(4), 1727–1742; https://doi.org/10.2741/A876
Published: 1 August 2002
(This article belongs to the Special Issue The structure and function of calcium release channels)
Abstract

The review examines the relationship between the structure of several ryanodine analogs and (A) binding, (B) channel conductance, and (C) ligand binding kinetics. Comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) are used to quantitatively assign structural correlations. Hydrogen bond donating (but not accepting) ability was found to be highly correlated with ligand affinity. Analysis of the correlation between hydrophobicity and ligand affinity indicates that, in general, deviation from the amphipathic nature of ryanodine weakens binding. Affinities and binding kinetics obtained in vivo are comparable to those obtained in the less-than-physiological in vitro conditions. Therefore, the structure-activity relationships surveyed are relevant to the living cell. The review presents arguments favoring the propositions that (A) the pyrrole is a major factor orienting the ligand in the receptor binding site and (B) that ryanoids alter ryanodine receptor function through allosteric mechanisms.

Keywords
Calcium
Release
Channel Ryanodine
Receptor
Ryanoids
CoMFA
CoMSIA QSAR
subconductance
kinetics
Review
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