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Per-glycosylation of the Surface-Accessible Lysines: One-Pot Aqueous Route to Stabilized Proteins with Native Activity

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Per-glycosylation of the Surface-Accessible Lysines : One-Pot Aqueous Route to Stabilized Proteins with Native Activity. / Walther, Raoul; Monge, Pere; Pedersen, Andreas; Benderoth, Anja; Pedersen, Jannik; Farzadfard, Azad; Mandrup, Ole; Howard, Kenneth; Otzen, Daniel; Zelikin, Alexander N.

In: ChemBioChem, Vol. 22, No. 14, 07.2021, p. 2478-2485.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Author

Walther, Raoul ; Monge, Pere ; Pedersen, Andreas ; Benderoth, Anja ; Pedersen, Jannik ; Farzadfard, Azad ; Mandrup, Ole ; Howard, Kenneth ; Otzen, Daniel ; Zelikin, Alexander N. / Per-glycosylation of the Surface-Accessible Lysines : One-Pot Aqueous Route to Stabilized Proteins with Native Activity. In: ChemBioChem. 2021 ; Vol. 22, No. 14. pp. 2478-2485.

Bibtex

@article{5584cdd3f5a14b498f264112db2470b4,
title = "Per-glycosylation of the Surface-Accessible Lysines: One-Pot Aqueous Route to Stabilized Proteins with Native Activity",
abstract = "Chemical glycosylation of proteins is a powerful tool applied widely in biomedicine and biotechnology. However, it is a challenging undertaking and typically relies on recombinant proteins and site-specific conjugations. The scope and utility of this nature-inspired methodology would be broadened tremendously by the advent of facile, scalable techniques in glycosylation, which are currently missing. In this work, we investigated a one-pot aqueous protocol to achieve indiscriminate, surface-wide glycosylation of the surface accessible amines (lysines and/or N-terminus). We reveal that this approach afforded minimal if any change in the protein activity and recognition events in biochemical and cell culture assays, but at the same time provided a significant benefit of stabilizing proteins against aggregation and fibrillation - as demonstrated on serum proteins (albumins and immunoglobulin G, IgG), an enzyme (uricase), and proteins involved in neurodegenerative disease (α-synuclein) and diabetes (insulin). Most importantly, this highly advantageous result was achieved via a one-pot aqueous protocol performed on native proteins, bypassing the use of complex chemical methodologies and recombinant proteins.",
keywords = "glucuronidation, glycosylation, insulin, protein biochemistry, synuclein, INSULIN, PEPTIDES, PRODRUGS, STRATEGY, CHEMICAL-SYNTHESIS, GENERATION, ALBUMIN",
author = "Raoul Walther and Pere Monge and Andreas Pedersen and Anja Benderoth and Jannik Pedersen and Azad Farzadfard and Ole Mandrup and Kenneth Howard and Daniel Otzen and Zelikin, {Alexander N}",
note = "{\textcopyright} 2021 Wiley-VCH GmbH.",
year = "2021",
month = jul,
doi = "10.1002/cbic.202100228",
language = "English",
volume = "22",
pages = "2478--2485",
journal = "ChemBioChem",
issn = "1439-4227",
publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",
number = "14",

}

RIS

TY - JOUR

T1 - Per-glycosylation of the Surface-Accessible Lysines

T2 - One-Pot Aqueous Route to Stabilized Proteins with Native Activity

AU - Walther, Raoul

AU - Monge, Pere

AU - Pedersen, Andreas

AU - Benderoth, Anja

AU - Pedersen, Jannik

AU - Farzadfard, Azad

AU - Mandrup, Ole

AU - Howard, Kenneth

AU - Otzen, Daniel

AU - Zelikin, Alexander N

N1 - © 2021 Wiley-VCH GmbH.

PY - 2021/7

Y1 - 2021/7

N2 - Chemical glycosylation of proteins is a powerful tool applied widely in biomedicine and biotechnology. However, it is a challenging undertaking and typically relies on recombinant proteins and site-specific conjugations. The scope and utility of this nature-inspired methodology would be broadened tremendously by the advent of facile, scalable techniques in glycosylation, which are currently missing. In this work, we investigated a one-pot aqueous protocol to achieve indiscriminate, surface-wide glycosylation of the surface accessible amines (lysines and/or N-terminus). We reveal that this approach afforded minimal if any change in the protein activity and recognition events in biochemical and cell culture assays, but at the same time provided a significant benefit of stabilizing proteins against aggregation and fibrillation - as demonstrated on serum proteins (albumins and immunoglobulin G, IgG), an enzyme (uricase), and proteins involved in neurodegenerative disease (α-synuclein) and diabetes (insulin). Most importantly, this highly advantageous result was achieved via a one-pot aqueous protocol performed on native proteins, bypassing the use of complex chemical methodologies and recombinant proteins.

AB - Chemical glycosylation of proteins is a powerful tool applied widely in biomedicine and biotechnology. However, it is a challenging undertaking and typically relies on recombinant proteins and site-specific conjugations. The scope and utility of this nature-inspired methodology would be broadened tremendously by the advent of facile, scalable techniques in glycosylation, which are currently missing. In this work, we investigated a one-pot aqueous protocol to achieve indiscriminate, surface-wide glycosylation of the surface accessible amines (lysines and/or N-terminus). We reveal that this approach afforded minimal if any change in the protein activity and recognition events in biochemical and cell culture assays, but at the same time provided a significant benefit of stabilizing proteins against aggregation and fibrillation - as demonstrated on serum proteins (albumins and immunoglobulin G, IgG), an enzyme (uricase), and proteins involved in neurodegenerative disease (α-synuclein) and diabetes (insulin). Most importantly, this highly advantageous result was achieved via a one-pot aqueous protocol performed on native proteins, bypassing the use of complex chemical methodologies and recombinant proteins.

KW - glucuronidation

KW - glycosylation

KW - insulin

KW - protein biochemistry

KW - synuclein

KW - INSULIN

KW - PEPTIDES

KW - PRODRUGS

KW - STRATEGY

KW - CHEMICAL-SYNTHESIS

KW - GENERATION

KW - ALBUMIN

U2 - 10.1002/cbic.202100228

DO - 10.1002/cbic.202100228

M3 - Journal article

C2 - 33998129

VL - 22

SP - 2478

EP - 2485

JO - ChemBioChem

JF - ChemBioChem

SN - 1439-4227

IS - 14

ER -