A Fluorine Scan of Thrombin Inhibitors to Map the Fluorophilicity/Fluorophobicity of an Enzyme Active Site: Evidence for CF⋅⋅⋅CO Interactions

Abstract

A highly fluorophilic environment comprising the HCαCO unit of Asn 98 in the active site of thrombin was identified by X-ray crystallography of a complex formed between the enzyme and a synthetic inhibitor (see partial X-ray structure, distances are in Angstroms). Short CF⋅⋅⋅HCα and CF⋅⋅⋅CO contacts involving HCαCO fragments were also frequently observed in small-molecule X-ray crystal structures.