In:
ChemBioChem, Wiley, Vol. 22, No. 22 ( 2021-11-16), p. 3199-3207
Abstract:
Site‐specific protein modifications are vital for biopharmaceutical drug development. Gluconoylation is a non‐enzymatic, post‐translational modification of N‐terminal HisTags. We report high‐yield, site‐selective in vitro α‐aminoacylation of peptides, glycoproteins, antibodies, and virus‐like particles (VLPs) with azidogluconolactone at pH 7.5 in 1 h. Conjugates slowly hydrolyse, but diol‐masking with borate esters inhibits reversibility. In an example, we multimerise azidogluconoylated SARS‐CoV‐2 receptor‐binding domain (RBD) onto VLPs via click‐chemistry, to give a COVID‐19 vaccine. Compared to yeast antigen, HEK‐derived RBD was immunologically superior, likely due to observed differences in glycosylation. We show the benefits of ordered over randomly oriented multimeric antigen display, by demonstrating single‐shot seroconversion and best virus‐neutralizing antibodies. Azidogluconoylation is simple, fast and robust chemistry, and should accelerate research and development.
Type of Medium:
Online Resource
ISSN:
1439-4227
,
1439-7633
DOI:
10.1002/cbic.202100381
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
2020469-3
SSG:
12
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