The pattern of fluorine substitution affects binding affinity in a small library of fluoroaromatic inhibitors for carbonic anhydrase.
[formula: see text] A library of fluoroaromatic inhibitors of carbonic anhydrase has been found to bind in a manner dependent on both hydrophobicity and the pattern of substitution of the fluoroaromatic ring. All of the compounds in the library bind to the protein with Kd < 3 nM. We have inferred two distinct binding modes from our data, which suggest two types of interactions that should be considered when designing fluorinated drugs.
Doyon
J B
JB
Department of Chemistry, Swarthmore College, Pennsylvania 19081-1397, USA.
Jain
A
A
D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism; D003461:Crystallography; D005461:Fluorine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D009795:Octanes; D013329:Structure-Activity Relationship; D014867:Water
D002257:Carbonic Anhydrase Inhibitors; D009795:Octanes; D014867:Water; D005461:Fluorine; C026728:octane