Sialylation is an important parameter that could affect function and pharmacokinetics of therapeutic glycoproteins. For example, α2,6-sialylation is known to enhance monoclonal antibody (mAb) ADCC and anti-inflammatory activity. In order to improve the stability and effector function of antibody, we designed a sialidase-resistant N-glycan with terminal sialic acid derivative, which contains an axial fluorine substituent at 3-position (3Fax-Neu5Ac). Chemical synthesis of the a2,6-3Fax-Neu5Ac-sialylated complex-type (a2,6-3Fax-SCT) bi-antennary N-glycan, chemoenzymatic synthesis of the a2,6-3Fax-SCT glycoform of rituximab, as well as in vitro activities, and sialidase-resistance of the new glycoform of rituximab will be disclosed for the first time (Figure 1). Our findings open up new opportunities for the development of therapeutic glycoproteins with improved pharmacokinetic parameters.

Synthesis of the antibody glycoform with a2,6-linked 3Fax-Neu5Ac

2019 Fall National Meeting

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