4y0y

Publication Abstract from PubMed

Introducing fluorine into molecules has a wide range of effects on their physicochemical properties, often desirable but in most cases unpredictable. The fluorine atom imparts the C-F bond with low polarizability and high polarity, and significantly affects the behavior of neighboring functional groups, in a covalent or noncovalent manner. Here, we report that fluorine, present in the form of a single fluoroalkyl amino acid side chain in the P1 position of the well-characterized serine-protease inhibitor BPTI, can fully restore inhibitor activity to a mutant that contains the corresponding hydrocarbon side chain at the same site. High resolution crystal structures were obtained for four BPTI variants in complex with bovine beta-trypsin, revealing changes in the stoichiometry and dynamics of water molecules in the S1 subsite. These results demonstrate that the introduction of fluorine into a protein environment can result in "chemical complementation" that has a significantly favorable impact on protein-protein interactions.

Fluorine teams up with water to restore inhibitor activity to mutant BPTI.,Ye S, Loll B, Berger AA, Mulow U, Alings C, Wahl MC, Koksch B Chem Sci. 2015 Sep 1;6(9):5246-5254. doi: 10.1039/c4sc03227f. Epub 2015 Jun 12. PMID:29449928^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.