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Updated: May 14, 2025

Determination of the Gas-phase Acidities of Oligopeptides
Published on: June 24, 2013
Quantum Evaluation of a Comprehensive Set of Carboxylic Acid Bioisosteres: Gas versus Solvated Phases
1College of Medicine and Health Sciences, Department of Biochemistry and Molecular Biology, United Arab Emirates University, P.O. Box: AlAin 15551, United Arab Emirates.
Abstract:
In drug design, bioisosterism is used to enhance the pharmacokinetic and pharmacodynamic properties of a drug molecule while maintaining its biological activity. This study investigates the use of a quantum tool, namely, the average electron density (AED) tool, in evaluating 54 experimentally tested nonclassical carboxylic acid bioisosteres. In total, 65 bioisosteres were considered, including both R and S enantiomers for 11 chiral moieties. The AED values of all bioisosteric moieties deviate by up to 32% compared to the carboxylic acid group, regardless of the medium, whether in the gas phase or implicitly solvated with water. This suggests that a 32% deviation threshold is reasonable for classifying potential carboxylic acid bioisosteres.
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