Glycosaminoglycan microarrays for studying glycosaminoglycan-protein systems

More than 3000 proteins are now known to bind to glycosaminoglycans (GAGs). Yet, GAG - protein systems are rather poorly understood in terms of selectivity of recognition, molecular mechanism of action, and translational promise. High-throughput screening (HTS) technologies are critically needed for studying GAG biology and developing GAG -based therapeutics. Microarrays, developed within the past two decades, have now improved to the point of being the preferred tool in the HTS of biomolecules. GAG microarrays, in which GAG sequences are immobilized on slides, while similar to other microarrays, have their own sets of challenges and considerations. GAG microarrays are rapidly becoming the first choice in studying GAG - protein systems. Here, we review different modalities and applications of GAG microarrays presented to date. We discuss advantages and disadvantages of this technology, explain covalent and non-covalent immobilization strategies using different chemically reactive groups, and present various assay formats for qualitative and quantitative interpretations, including selectivity screening, binding affinity studies, competitive binding studies etc. We also highlight recent advances in implementing this technology, cataloging of data, and project its future promise. Overall, the technology of GAG microarray exhibits enormous potential of evolving into more than a mere screening tool for studying GAG - protein systems.