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

Raoul Walther, Pere Monge, Andreas Pedersen, Anja Benderoth, Jannik Pedersen, Azad Farzadfard, Ole Mandrup, Kenneth Howard, Daniel Otzen, Alexander N Zelikin*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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.

OriginalsprogEngelsk
TidsskriftChemBioChem
Vol/bind22
Nummer14
Sider (fra-til)2478-2485
Antal sider8
ISSN1439-4227
DOI
StatusUdgivet - jul. 2021

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