Use of Fluorinated Functionality in Enzyme Inhibitor Development: Mechanistic and Analytical Advantages.

ABSTRACT: On the one hand, owing to its electronegativity, relatively small size, and notable leaving group ability from anionic intermediates, fluorine offers unique opportunities for mechanism-based enzyme inhibitor design. On the other, the "bio-orthogonal" and NMR-active 19-fluorine nucleus allows the bioorganic chemist to follow the mechanistic fate of fluorinated substrate analogues or inhibitors as they are enzymatically processed. This article takes an overview of the field, highlighting key developments along these lines. It begins by highlighting new screening methodologies for drug discovery that involve appropriate tagging of either substrate or the target protein itself with (19)F-markers, that then report back on turnover and binding, respectively, via an the NMR screen. Taking this on

SUBMITTER: Berkowitz DB 

PROVIDER: S-EPMC2598403 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature