Glycosylation Improves the Proteolytic Stability of Exenatide

Chaitra Chandrashekar; Yuji Nishiuchi; Barbara Fam White; Yanni Arsenakis; Feng Lin; Samantha M. McNeill; Peishen Zhao; Sam van Dun; Anna Koijen; Yasuhiro Kajihara; Denise Wootten; Leendert J. van den Bos; John D. Wade; Mohammed Akhter Hossain

doi:10.1021/acs.bioconjchem.3c00120

Glycosylation Improves the Proteolytic Stability of Exenatide

Chaitra Chandrashekar, Yuji Nishiuchi, Barbara Fam White, Yanni Arsenakis, Feng Lin, Samantha M. McNeill, Peishen Zhao, Sam van Dun, Anna Koijen, Yasuhiro Kajihara, Denise Wootten, Leendert J. van den Bos, John D. Wade, Mohammed Akhter Hossain

Drug Discovery Biology

Research output: Contribution to journal › Article › Research › peer-review

4 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1014-1018
Number of pages	5
Journal	Bioconjugate Chemistry
Volume	34
Issue number	6
DOIs	https://doi.org/10.1021/acs.bioconjchem.3c00120
Publication status	Published - 21 Jun 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/acs.bioconjchem.3c00120

Cite this

@article{ffe8800f57c441b5ad42008dd6208e59,

title = "Glycosylation Improves the Proteolytic Stability of Exenatide",

abstract = "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.",

author = "Chaitra Chandrashekar and Yuji Nishiuchi and White, {Barbara Fam} and Yanni Arsenakis and Feng Lin and McNeill, {Samantha M.} and Peishen Zhao and {van Dun}, Sam and Anna Koijen and Yasuhiro Kajihara and Denise Wootten and {van den Bos}, {Leendert J.} and Wade, {John D.} and Hossain, {Mohammed Akhter}",

note = "Funding Information: This study was funded by NHMRC Ideas Grants (APP1182996, APP2001278, and APP2010781) and an ARC Linkage grant (LP170101085) to M.A.H and J.D.W. studies at the FNI were supported by the Victorian Government{\textquoteright}s Operational Infrastructure Support Program. Publisher Copyright: {\textcopyright} 2023 American Chemical Society.",

year = "2023",

month = jun,

day = "21",

doi = "10.1021/acs.bioconjchem.3c00120",

language = "English",

volume = "34",

pages = "1014--1018",

journal = "Bioconjugate Chemistry",

issn = "1043-1802",

publisher = "American Chemical Society",

number = "6",

}

TY - JOUR

T1 - Glycosylation Improves the Proteolytic Stability of Exenatide

AU - Chandrashekar, Chaitra

AU - Nishiuchi, Yuji

AU - White, Barbara Fam

AU - Arsenakis, Yanni

AU - Lin, Feng

AU - McNeill, Samantha M.

AU - Zhao, Peishen

AU - van Dun, Sam

AU - Koijen, Anna

AU - Kajihara, Yasuhiro

AU - Wootten, Denise

AU - van den Bos, Leendert J.

AU - Wade, John D.

AU - Hossain, Mohammed Akhter

N1 - Funding Information: This study was funded by NHMRC Ideas Grants (APP1182996, APP2001278, and APP2010781) and an ARC Linkage grant (LP170101085) to M.A.H and J.D.W. studies at the FNI were supported by the Victorian Government’s Operational Infrastructure Support Program. Publisher Copyright: © 2023 American Chemical Society.

PY - 2023/6/21

Y1 - 2023/6/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85160748906&partnerID=8YFLogxK

U2 - 10.1021/acs.bioconjchem.3c00120

DO - 10.1021/acs.bioconjchem.3c00120

M3 - Article

C2 - 37192432

AN - SCOPUS:85160748906

SN - 1043-1802

VL - 34

SP - 1014

EP - 1018

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

IS - 6

ER -

Glycosylation Improves the Proteolytic Stability of Exenatide

Abstract

UN SDGs

Access to Document

Other files and links

Cite this