posted on 2019-04-10, 00:00authored byHong-Jay Lo, Larissa Krasnova, Supriya Dey, Ting Cheng, Haitian Liu, Tsung-I Tsai, Kevin Binchia Wu, Chung-Yi Wu, Chi-Huey Wong
Fluorinated glycosides are known
to resist the glycosidase-catalyzed
glycosidic bond cleavage; however, the synthesis of such glycans,
especially 3-fluoro-sialic acid (3F-Neu5Ac) containing sialosides,
has been a major challenge. Though the enzymatic synthesis of α-2,3-linked
3F-sialosides was reported, until recently there has not been any
effective method available for the synthesis of 3F-sialosides in the
α-2,6-linkage. In order to understand the biological effect
of such modification, we report here a chemical synthesis of 3Fax-Neu5Ac-α2,6-Gal as a building block for the assembly
of 3Fax-Neu5Ac-containing sialosides and a representative
homogeneous antibody glycoform. Our results showed that the sialosides
are stable under sialidase catalysis and the rituximab glycoform with
a sialylated complex-type biantennary glycan terminated with 3Fax-Neu5Ac in the α-2,6-linkage (α2,6-F-SCT) has
a similar binding avidity as its parent glycoform. These findings
open up new opportunities for the development of therapeutic glycoproteins
with improved pharmacokinetic parameters.