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How formaldehyde reacts with amino acids

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journal contribution
posted on 03.08.2020, 09:07 by Jos JAG Kamps, Richard J Hopkinson, Christopher J Schofield, Timothy DW Claridge
Formaldehyde is a biological electrophile produced via processes including enzymatic demethylation. Despite its apparent simplicity, the reactions of formaldehyde with even basic biological components are incompletely defined. Here we report NMR-based studies on the reactions of formaldehyde with common proteinogenic and other nucleophilic amino acids. The results reveal formaldehyde reacts at different rates, forming hydroxymethylated, cyclised, cross-linked, or disproportionated products of varying stabilities. Of the tested common amino acids, cysteine reacts most efficiently, forming a stable thiazolidine. The reaction with lysine is less efficient; low levels of an Nε-methylated product are observed, raising the possibility of non-enzymatic lysine methylation by formaldehyde. Reactions with formaldehyde are faster than reactions with other tested biological carbonyl compounds, and the adducts are also more stable. The results reveal reactions of formaldehyde with amino acids, and by extension peptides and proteins, have potential roles in healthy and diseased biology, as well as in evolution.

Funding

We thank the Wellcome Trust and Cancer Research UK for funding. We thank the Engineering and Physical Sciences Research Council for a studentship to JJAGK via the Centre for Doctoral Training in Synthesis for Biology and Medicine (EP/L015838/1), and a Clarendon Scholarship.

History

Citation

Kamps, J.J.A.G., Hopkinson, R.J., Schofield, C.J. et al. How formaldehyde reacts with amino acids. Commun Chem 2, 126 (2019). https://doi.org/10.1038/s42004-019-0224-2

Version

VoR (Version of Record)

Published in

Communications Chemistry

Volume

2

Issue

1

Pagination

126

Publisher

Nature Research

issn

2399-3669

eissn

2399-3669

Acceptance date

23/09/2019

Copyright date

2019

Available date

03/08/2020

Language

English

Publisher version

https://www.nature.com/articles/s42004-019-0224-2