Loss of fluorine during crosslinking by the biarylitide P450 Blt proceeds due to restricted peptide orientation

The biarylitide crosslinking enzyme P450 can perform crosslinking between -F-Tyr-3 and His-5 residues within peptide substrates with concomitant and specific loss of fluorine. Our investigations suggest that a small intrinsic preference for coupling to fluorine is magnified by the binding of the pep...

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Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2024-11, Vol.60 (94), p.13951-13954
Main Authors: Zhao, Yongwei, Gullick, Jemma, Hansen, Mathias H, Coe, Laura, Treisman, Maxine, Schittenhelm, Ralf B, McKay, Alasdair, Murray, Lauren A M, Tailhades, Julien, De Voss, James J, Krenske, Elizabeth H, Cryle, Max J
Format: Article
Language:English
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Summary:The biarylitide crosslinking enzyme P450 can perform crosslinking between -F-Tyr-3 and His-5 residues within peptide substrates with concomitant and specific loss of fluorine. Our investigations suggest that a small intrinsic preference for coupling to fluorine is magnified by the binding of the peptide in a specific orientation that enforces the loss of fluorine during peptide crosslinking, likely a two-step reaction mechanism involving the non-enzyme catalysed reductive elimination of fluoride.
ISSN:1359-7345
1364-548X
DOI:10.1039/D4CC04092A