Understanding viral neuraminidase inhibition by substituted difluorosialic acids
S Weck1, K Robinson, M R Smith
1Departments of Chemistry and Biochemistry, University of British Columbia, Vancouver, BC V6T 1Z1, Canada. withers@chem.ubc.ca.
Chemical Communications (Cambridge, England)
|January 15, 2015
Abstract:
Mechanism-based inhibition of influenza neuraminidases by difluorosialic acids (DFSA) is not only rendered highly specific by incorporation of 4-amino or 4-guanidine substituents but also the half-life for reactivation is greatly increased. Measurement of rate constants for spontaneous hydrolysis of a series of such substituted DFSAs reveals, surprisingly, that inherent inductive effects play very little role in this rate reduction and that interactions with the enzyme are more important.
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