Glycosylation Improves the Proteolytic Stability of Exenatide.

2023-05-16

Chandrashekar, Chaitra

Nishiuchi, Yuji

White, Barbara Fam

Arsenakis, Yanni

Lin, Feng

McNeill, Samantha M

Zhao, Peishen

van Dun, Sam

Koijen, Anna

Kajihara, Yasuhiro

Wootten, Denise

van den Bos, Leendert J

Wade, John D

Hossain, Mohammed Akhter

Journal Article

0000-0002-0288-5952

0000-0001-7662-5187

#PLACEHOLDER_PARENT_METADATA_VALUE#

#PLACEHOLDER_PARENT_METADATA_VALUE#

0000-0001-5735-4924

#PLACEHOLDER_PARENT_METADATA_VALUE#

0000-0003-0185-0595

#PLACEHOLDER_PARENT_METADATA_VALUE#

#PLACEHOLDER_PARENT_METADATA_VALUE#

0000-0002-6656-2394

0000-0003-4563-1642

#PLACEHOLDER_PARENT_METADATA_VALUE#

0000-0002-1352-6568

0000-0002-9961-0006

10.1021/acs.bioconjchem.3c00120

Exenatide was the first marketed GLP-1 receptor agonist for the treatment of type 2 diabetes. Modification to the chemical structure or the formulation has the potential to increase the stability of exenatide. We introduced human complex-type sialyloligosaccharide to exenatide at the native Asn28 position. The synthesis was achieved using both solid phase peptide synthesis (SPPS) and Omniligase-1-mediated chemoenzymatic ligation. The results demonstrate that glycosylation increases the proteolytic stability of exenatide while retaining its full biological activity.

link

Bioconjugate Chemistry 2023-05-16, 34(6)

Bioconjugate Chemistry

1520-4812