Phenylboronic-acid-based carbohydrate binders as antiviral therapeutics: Bisphenylboronic acids

Paul C. Trippier, Jan Balzarini, Christopher McGuigan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)129-142
Number of pages14
JournalAntiviral Chemistry and Chemotherapy
Volume21
Issue number3
DOIs
StatePublished - Jan 28 2011

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Boronic Acids
Antiviral Agents
HIV-1
Carbohydrates
Viruses
Acids
Structure-Activity Relationship
Polysaccharides
Therapeutics
benzeneboronic acid
Lead
Simian immunodeficiency virus gp120 protein

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Virology

Cite this

Phenylboronic-acid-based carbohydrate binders as antiviral therapeutics : Bisphenylboronic acids. / Trippier, Paul C.; Balzarini, Jan; McGuigan, Christopher.

In: Antiviral Chemistry and Chemotherapy, Vol. 21, No. 3, 28.01.2011, p. 129-142.

Research output: Contribution to journalArticle

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