Keenan, Tessa, Spears, Richard J, Akkad, Saeed orcid.org/0000-0002-7271-0496 et al. (9 more authors) (2021) A tale of two bioconjugations : pH controlled divergent reactivity of protein a-oxo aldehydes in competing a-oxo-Mannich and catalyst-free aldol ligations. ACS Chemical Biology. pp. 2387-2400. ISSN 1554-8937
Abstract
Site-selective chemical methods for protein bioconjugation have revolutionised the fields of cell and chemical biology through the development of novel protein/enzyme probes bearing fluorescent, spectroscopic or even toxic cargos. Herein we report two new methods for the bioconjugation of a-oxo aldehyde handles within proteins using small molecule aniline and/or phenol probes. The ‘a-oxo-Mannich’ and ‘catalyst-free aldol’ ligations both compete for the electrophilic a-oxo aldehyde which displays pH divergent reactivity proceeding through the “Mannich” pathway at acidic pH to afford bifunctionalised bioconjugates, and the “catalyst-free aldol” pathway at neutral pH to afford monofunctionalised bioconjugates. We explore the substrate scope and utility of both these bioconjugations in the construction of neoglycoproteins, in the process formulating a mechanistic rationale for how both pathways intersect with each other at different reaction pH.
Metadata
Item Type: | Article | ||||
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 American Chemical Society. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details |
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Keywords: | Aldehydes/chemistry, Aniline Compounds/chemistry, Catalysis, Hydrogen-Ion Concentration, Mannich Bases/chemistry, Peptides/chemistry, Proteins/chemistry | ||||
Dates: |
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Institution: | The University of York | ||||
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
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Funding Information: |
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Depositing User: | Pure (York) | ||||
Date Deposited: | 22 Oct 2021 16:00 | ||||
Last Modified: | 14 Apr 2024 23:14 | ||||
Published Version: | https://doi.org/10.1021/acschembio.1c00531 | ||||
Status: | Published | ||||
Refereed: | Yes | ||||
Identification Number: | https://doi.org/10.1021/acschembio.1c00531 |
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