Title

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

Funding Source

National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI) of the NIH

Grant Number

5 P20 GM103424-15,K12 HL141954,3 P20 GM103424-15S1

Department

College of Pharmacy

Document Type

Article

Publication Date

2020

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 re-cently 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.

Comments

DOI: 10.2174/0929867325666181120101147

PubMed ID: 30457046

Funding text

Dr. Rami A. Al-Horani has been supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) under grant numbers 5 P20 GM103424-15 and 3 P20 GM103424-15S1. Dr. Daniel K. Afosah has been supported by grant K12 HL141954 from the National Heart, Lung, and Blood Institute (NHLBI) of the NIH. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.


Link to Full Text

Share

COinS