Volume 828, 30 May 2014, Pages 61–69
Substituent effects on the binding of natural product anthocyanidin inhibitors to influenza neuraminidase with mass spectrometry
Highlights
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- MALDI MS approach identifies differences in binding affinity of similar inhibitors.
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- Relative reduction in ion signal is in accord with their inhibitory potential.
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- Approach is a sensitive and high-throughput molecular screen of drug binding.
Abstract
The
binding of three closely related anthocyanins within the 430-cavity of
influenza neuraminidase is studied using a combination of mass
spectrometry and molecular docking. Despite their similar structures,
which differ only in the number and position of the hydroxyl
substituents on the phenyl group attached to the chromenylium ring,
subtle differences in their binding characteristics are revealed by mass
spectrometry and molecular docking that are in accord with their
inhibitory properties by neuraminidase inhibition assays. The cyanidin
and delphinidin, with the greatest number of hydroxyl groups, bind more
strongly and are better inhibitors than pelargonidin that contains a
lone hydroxyl group at the 4′ position. The study demonstrates, for the
first time, the sensitivity of the mass spectrometry based approach for
investigating the molecular basis and relative affinity of antiviral
inhibitors, with subtly different structures, to their target protein.
It has broader application for the screening of other protein
interactions more generally with reasonable high-throughput.
Graphical abstract
Keywords
- Anthocyanidin;
- Inhibitor;
- Influenza;
- Neuraminidase;
- MALDI;
- Mass spectrometry
- Corresponding author. Tel.:
+61 2 9351 4140.
Copyright © 2014 Elsevier B.V. All rights reserved.
