Heparan sulfates (HSs) are complex sulfated polysaccharides present on almost all cell surfaces in multicellular organisms. They have variant structures which represent a molecular code that is a subset of the glycome called the ‘heparanome’. These sulfation patterns confer the ability to interact selectively with a wide interactome of proteins that influences many cellular processes important in the development, regulation and repair of tissues. Understanding the chemical biology of these enigmatic molecules is now becoming possible through a variety of tools, reagents and approaches including saccharide libraries, microarray methods and novel sequencing approaches [1]. We are developing and exploiting semi-synthetic and synthetic chemistry strategies to produce targeted libraries for activity screening to decode the molecular basis of the functional diversity of HS [2,3]. This has yielded new insights into this code in a variety of biological contexts, including neural development, degeneration and repair, and cancer metastasis. This has led to a translational pathway of biomedical applications, including discovery of novel drug leads for Alzheimers disease [4] and cancer metastasis, and potential interventions to improve neural cell transplantation for nerve repair [5].
References: [1] Turnbull, JE (2010) Biochem Soc. Trans. 38, 1356-1360; [2] AK Powell et al (2010) Nature Protocols 5, 829-841; [3] R Schwörer, OV. Zubkova, JE. Turnbull* and PC. Tyler*.(2013) Chemistry European Journal. (in press); [4] Patey, SJ et al J Med Chem 49, 6129-6132.; [4] JR Higginson et al (2012) Journal of Neuroscience 32, 15902-15912.
