Fluorine Replaces a Hydroxyl

The van der Waals radii of oxygen and fluorine atoms and the polarity of the C—F and C—O bonds are close. It can be assumed that replacement of a hydroxyl by a fluorine atom in a substrate of an enzyme does not impede recognition by the enzyme and can eventually transform the substrate into a potential inhibitor. 

1 Inhibition of Dehydroquinase Type II Dehydroquinase type II is an important enzyme in the shikimic and quinic routes. It ensures the reversible conversion of 3-dehydroquinate (DHQ) into 3-dehydroshrkimate (DHS). Ehmination of the hydroxyl is assisted by an acid/base catalysis that is associated with a residue of the active site. 

3 Fluorinated Analogues of Substrates in Which Fluorine is Not Directly Involved in Inhibition 

In contrast with previous examples (cf. Sections 7.1.1 and 7.1.2), fluorine atoms are not directly involved in the enzymatic reaction. They are useful to improve the inhibitor properties of the substrate analogue. 

Phosphonates that do not undergo cleavage by phosphatases can also be used as stable analogues of phosphorylated molecules, and thus they can be considered as substrates. Various applications are given at the end of this section.  

---