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Fluorine-induced polarity increases inhibitory activity of BPTI towards chymotrypsin

Jakob Leppkes, Nicole Dimos, Bernhard Loll, Thomas Hohmann, Michael Dyrks, Ariane Wieseke, Bettina G. Keller, and Beate Koksch – 2022

Substituting the P1 position in bovine pancreatic trypsin inhibitor (BPTI) is known to heavily influence its inhibitory activity towards serine proteases. Side-chain fluorinated aliphatic amino acids have been shown to alter numerous properties of peptides and proteins and thus are of interest in the context of BPTI. In our study, we systematically investigated the site-specific incorporation of non-canonical amino acids into BPTI by microwave-assisted solid-phase peptide synthesis (SPPS). Inhibitor activity of the variants was tested towards the serine protease α-chymotrypsin. We observed enhanced inhibition of two fluorinated BPTIs compared to wild type and hydrocarbon variants. To further investigate the complexes, we performed X-ray structure analysis. Our findings underline the power fluorine offers as a tool in protein engineering to beneficially alter the effects on phenomena as protein–protein interactions.

Title
Fluorine-induced polarity increases inhibitory activity of BPTI towards chymotrypsin
Author
Jakob Leppkes, Nicole Dimos, Bernhard Loll, Thomas Hohmann, Michael Dyrks, Ariane Wieseke, Bettina G. Keller, and Beate Koksch
Date
2022-05-19
Source(s)
Citation
RSC Chem. Biol., 2022, https://doi.org/10.1039/D2CB00018K
Language
eng
Type
Text
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