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Sulfated Non-Saccharide Glycosaminoglycan Mimetics as Novel Drug Discovery Platform for Various Pathologies

Author(s):

Daniel K. Afosah and Rami A. Al-Horani*   Pages 1 - 35 ( 35 )

Abstract:


Glycosaminoglycans (GAGs) are very complex, natural anionic polysaccharides. They are polymers of repeating disaccharide units of uronic acid and hexosamine residues. Owing to their template-free, spatiotemporally controlled, and enzyme-mediated biosyntheses, GAGs possess enormous polydispersity, heterogeneity, and structural diversity which often translate into multiple biological roles. It is well documented that GAGs contribute to physiological and pathological processes by binding to proteins including serine proteases, serpins, chemokines, growth factors, and microbial proteins. Despite advances in the GAG field, the GAG–protein interface remains largely unexploited by drug discovery programs. Thus, non-saccharide glycosaminoglycan mimetics (NSGMs) have been rationally developed as a novel class of sulfated molecules that modulate GAG–protein interface to promote various biological outcomes of substantial benefit to human health. In this review, we describe the chemical, biochemical, and pharmacological aspects of recently reported NSGMs and highlight their therapeutic potentials as structurally and mechanistically novel anti-coagulants, anti-cancer agents, anti-emphysema agents, and anti-viral agents. We also describe the challenges that complicate their advancement and describe ongoing efforts to overcome these challenges with the aim of advancing the novel platform of NSGMs to clinical use.

Keywords:

Glycosaminoglycans, Sulfated molecules, Non-saccharide glycosaminoglycan mimetics, Anticoagulants, Anticancers, Antivirals

Affiliation:

Department of Medicinal Chemistry and Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia 23219, Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana 70125



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