Probing the Interaction of Dengue Virus Envelope Protein with Heparin: Assessment of Glycosaminoglycan-Derived Inhibitors
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Authors
Marks, R.M.
Lu, H.
Sundaresan, R.
Toida, T.
Suzuki, A.
Imanari, T.
Hernaiz, M.J.
Linhardt, Robert J.
Issue Date
2001-06-21
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
A structure-activity relationship study was carried out to facilitate development of inhibitors of dengue virus infectivity. Previous studies demonstrated that a highly charged heparan sulfate, a heparin-like glycosaminoglycan found on the cell surface, serves as a receptor for dengue virus by binding to its envelope protein. Interventions that disrupt this binding effectively inhibit infectivity. A competitive binding assay was developed to screen polyanionic compounds for activity in preventing binding of dengue virus envelope protein to immobilized heparin; compounds tested included drugs, excipients, and larger glycosaminoglycans and their semisynthetic derivatives. Results of this competitive binding assay were used to select agents for detailed evaluation of interactions by surface plasmon resonance spectroscopy, which afforded binding on-rates, off-rates, and dissociation constants. From these data, an understanding of the structural requirements for polyanion binding to dengue virus envelope protein has been established.
Description
Journal of Medicinal Chemistry, 44, 2178-2187
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Probing the Interaction of Dengue Virus Envelope Protein with Heparin: Assessment of Glycosaminoglycan-Derived Inhibitors, R.M. Marks, H. Lu, R. Sundaresan, T. Toida, A. Suzuki, T. Imanari, M.J. Hernaiz, R. J. Linhardt, Journal of Medicinal Chemistry, 44, 2178-2187, 2001.
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Volume
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PubMed ID
DOI
ISSN
222623