Linear Free Energy Relationships Implicate Three Modes Of Binding For Fluoroaromatic Inhibitors To A Mutant Of Carbonic Anhydrase II

Document Type

Article

Publication Date

5-4-2000

Published In

Organic Letters

Abstract

Linear free energy relationships between binding affinity and hydrophobicity for a library of fluoroaromatic inhibitors of F131V carbonic anhydrase II (CA) implicate three modes of interaction. X-ray crystal structures suggest that F131 interacts with fluoroaromatic inhibitors, while P202, on the opposite side of the active site cleft, serves as the site of the hydrophobic contact in the case of the F131V mutant. 2-Fluorinated compounds bind more tightly, perhaps due to the field effect of the nearby fluorine on the acidity of the amide proton.

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