Zhang Xing, Xu Yongmei, Hsieh Po-Hung, Liu Jian, Lin Lei, Schmidt Eric P, Linhardt Robert J
Departments of Chemistry and Chemical Biology, Chemical and Biochemical Engineering, Biology, Biomedical Engineering, Rensselaer Polytechnic Institute, 110 8th Avenue, Troy, New York 12180, USA.
Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Org Biomol Chem. 2017 Feb 1;15(5):1222-1227. doi: 10.1039/c6ob02603f.
A heparin oligosaccharide having a completely natural structure was successfully synthesized through a chemoenzymatic approach using an unnatural glycosyl acceptor, p-nitrophenyl glucuronide (GlcA-pNP). The use of an inexpensive and commercially available GlcA-pNP acceptor facilitates oligosaccharide recovery and purification on C-18 resin during chemoenzymatic synthesis. Oligosaccharide chain extension and modification afforded a heptasaccharide with gluconic acid residues at its reducing and non-reducing ends. Treatment with periodate oxidation followed by Smith degradation or alkaline elimination resulted in the selective cleavage of vicinal diol-containing glucuronic acid residues affording highly sulfated heparin pentasaccharides having a completely natural structure. This methodology should facilitate the chemoenzymatic synthesis of a family of highly sulfated heparin oligosaccharides with unmodified structures for biological evaluation.
通过化学酶法，使用非天然糖基受体对硝基苯基葡糖醛酸（GlcA-pNP）成功合成了具有完全天然结构的肝素寡糖。使用廉价且市售的GlcA-pNP受体有助于在化学酶法合成过程中在C-18树脂上回收和纯化寡糖。寡糖链的延伸和修饰得到了一种在其还原端和非还原端具有葡萄糖酸残基的七糖。用过碘酸盐氧化，然后进行Smith降解或碱消除处理，导致含邻二醇的葡糖醛酸残基选择性裂解，得到具有完全天然结构的高度硫酸化的肝素五糖。该方法应有助于化学酶法合成一系列具有未修饰结构的高度硫酸化肝素寡糖用于生物学评价。
