Heparin is a mixture of sulfated linear polysaccharides of molecular weight ~16,000 Da with repeating disaccharide unit obtained from animal tissues. It is widely used as a clinical anticoagulant drug. Heparin exerts its anticoagulant activity by binding with antithrombin III (AT) through a specific pentasaccharide sequence, containing a non-sulfated uronic acid residue. Non-anticoagulant heparin (NACH) is a low molecular weight heparin (LMWH, average molecular weight ~5000 Da) prepared from heparin by periodate oxidation. Periodate oxidation cleaves the vicinal diols of the non-sulfated uronic acid residues in heparin, resulting in chain fragmentation through heparin’s AT-binding site resulting in a LMWH with low or no anticoagulant activity. In the current study, we used comprehensive structural analysis approaches including top-down (intact NACH chains), bottom-up analysis (oligosaccharides treated by only heparin lyase II and disaccharides treated by mixture of heparin lyases I, II, III) to understand the fine structure of NACH. Furthermore, potential applications of NACH were investigated using surface plasmon resonance (SPR) to screening several significant proteins closely related to variety of biological processes. These proteins included hepatocyte growth factor (HGF), fibroblast growth factors (FGFs) and tumor growth factors (TGFs), which play important roles in angiogenesis, tumorigenesis and tissue regeneration.

Structural analysis and potential applications of non-anticoagulant heparin

256th National Meeting (2018)

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