Phenylboronic-Acid-Based Carbohydrate Binders as Antiviral Therapeutics: Bisphenylboronic Acids

Abstract

Background: Carbohydrate-binding agents are considered as potential therapeutic agents for the inhibition of highly glycosylated enveloped viruses such as HIV type-1. Phenylboronic acids are well-known to bind the cis-diol functionality of carbohydrate structures, thereby identifying themselves as potential lead structures. Methods: Bisphenylboronic acids connected via a functionalized linker at variable length (1–13 atoms) bearing the binding boronic acid functionality at the three possible ring geometries relative to the linker have been investigated as probes for selective and non-selective saccharide sensors. Herein, we describe the compilation of a ‘linker-diverse’ compound library of bisphenylboronic acids and the determination of the structure–activity relationship versus a variety of enveloped viruses. Molecular modelling of the gp120 glycans of simian immunodeficiency virus was undertaken to ascertain a theoretical minimum length of the linker unit. Results: The compounds demonstrated no pronounced antiviral activity. The general low toxicity of the boronic acids became evident in this study, thereby justifying further studies. Conclusions: A higher concentration of phenylboronate functional groups per molecule, resulting in multivalency, might be necessary to bind with sufficient potency to HIV type-1 gp120 and to elicit an antiviral action.