Jiyuan Yang, Payel Datta, Ke Xia, Vitor H Pomin, Chunyu Wang, Mingqiang Qiao, Robert J Linhardt, Jonathan S Dordick, Fuming Zhang
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Inhibition of sulfated glycans on the binding of dengue virus envelope protein to heparin.
Dengue viruses (DENV) are transmitted to humans through mosquito bites and infect millions globally. DENV uses heparan sulfate (HS) for attachment and cell entry by binding the envelope protein to highly sulfated HS on target cells. Therefore, inhibiting the binding between DENV and HS could be a promising strategy for preventing DENV infection. In the current study, the interactions between DENV envelope protein (from Type 2 DENV) and heparin (a surrogate for HS) were analyzed using competition solution SPR. Results demonstrate that heparin binds to DENV envelope protein with high affinity (KD = 8.83 nM). Competitive Solution SPR assays using surface-immobilized heparin and a series of naturally-sourced and semi-synthetic sulfated glycans demonstrated significant inhibitory activity against the binding of DENV envelope proteins to heparin. This study of molecular interactions could provide insights into the development of therapeutics for DENV infection.
期刊介绍:
Glycoconjugate Journal publishes articles and reviews on all areas concerned with:
function, composition, structure, biosynthesis, degradation, interactions, recognition and chemo-enzymatic synthesis of glycoconjugates (glycoproteins, glycolipids, oligosaccharides, polysaccharides and proteoglycans), biochemistry, molecular biology, biotechnology, immunology and cell biology of glycoconjugates, aspects related to disease processes (immunological, inflammatory, arthritic infections, metabolic disorders, malignancy, neurological disorders), structural and functional glycomics, glycoimmunology, glycovaccines, organic synthesis of glycoconjugates and the development of methodologies if biologically relevant, glycosylation changes in disease if focused on either the discovery of a novel disease marker or the improved understanding of some basic pathological mechanism, articles on the effects of toxicological agents (alcohol, tobacco, narcotics, environmental agents) on glycosylation, and the use of glycotherapeutics.
Glycoconjugate Journal is the official journal of the International Glycoconjugate Organization, which is responsible for organizing the biennial International Symposia on Glycoconjugates.