Portal de Periódicos da CAPES

Facile chemoenzymatic synthesis of Lewis a (Lea) antigen in gram-scale and sialyl Lewis a (sLea) antigens containing diverse sialic acid forms

2018; Elsevier BV; Volume: 472; Linguagem: Inglês

10.1016/j.carres.2018.12.004

1873-426X

Nova Tasnima, Hai Yu, Xuebin Yan, Wanqing Li, An Xiao, Xi Chen,

Monoclonal and Polyclonal Antibodies Research

An efficient streamlined chemoenzymatic approach has been developed for gram-scale synthesis of Lewis a angtigen (LeaβProN3) and a library of sialyl Lewis a antigens (sLeaβProN3) containing different sialic acid forms. Intially, commercially available inexpensive N-acetylglucosamine (GlcNAc) was converted to its N'-glycosyl p-toluenesulfonohydrazide in one step. Followed by chemical glycosylation, GlcNAcβProN3 was synthesized using this protecting group-free method in high yield (82%). Sequential one-pot multienzyme (OPME) β1-3-galactosylation of GlcNAcβProN3 followed by OPME α1-4-fucosylation reactions produced target LeaβProN3 in gram-scale. Structurally diverse sialic acid forms was successfully introduced using a OPME sialylation reation containing a CMP-sialic acid synthetase and Pasteurella multocida α2-3-sialyltransferase 1 (PmST1) mutant PmST1 M144D with or without a sialic acid aldolase to form sLeaβProN3 containing naturally occurring or non-natural sialic acid forms in preparative scales.