TY - JOUR
T1 - Phenylboronic-acid-based carbohydrate binders as antiviral therapeutics
T2 - Bisphenylboronic acids
AU - Trippier, Paul C.
AU - Balzarini, Jan
AU - McGuigan, Christopher
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
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U2 - 10.3851/IMP1707
DO - 10.3851/IMP1707
M3 - Article
C2 - 21233534
AN - SCOPUS:78951488387
VL - 21
SP - 129
EP - 142
JO - Antiviral Chemistry and Chemotherapy
JF - Antiviral Chemistry and Chemotherapy
SN - 0956-3202
IS - 3
ER -