Heparan sulfates contain variant sulfation patterns which represent a molecular code that is a subset of the glycome called the ‘heparanome’. They confer the ability to interact selectively with a wide interactome of proteins, especially growth factors and matrix proteins, acting as “master regulators” which co-ordinate many cellular processes that are also relevant to disease processes.  We have been using chemical biology tools and glycomics approaches to decode the molecular basis of the functional diversity of HS in specific disease contexts. Furthermore, we have recently developed a novel MS-based shotgun sequencing strategy for HS saccharides, and a comprehensive HPLC method for HS disaccharide analysis that includes for the first time 3-O-sulfated variants. Applications of these various methods have yielded new insights into the pathophysiological functions of HS in neurodegeneration (AD), nerve repair, cancer metastasis, and also regulation of cancer stem cells. The work has also provided new synthetic chemistry and glycomimetic routes to novel heparin-based compounds which are undergoing translational development as novel drug discovery leads for Alzheimers disease, cancer, nerve repair and most recently Covid19. We have promising preclinical data on efficacy in mouse models, along with favourable data on safety, pharmacokinetics and oral delivery of these compounds. Data on these studies will be presented in the context of their potential as part of the next generation of heparin therapeutics.

Next generation heparins and mimetics: Elucidating and targeting heparan sulfate functions for therapeutic benefit

ACS Fall 2021

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