Expanding the fluorous arsenal: tetrafluorinated phenylalanines for protein design.
Tetrafluorinated phenylalanines were incorporated into villin headpiece subdomain HP35, and their energetic contribution to protein stability was evaluated. In comparison to pentafluoro-phenylalanines, HP35 variants harboring tetrafluorinated phenylalanines exhibit increased thermal and thermodynamic stability by a large margin. The favorable stabilization is attributed to the electrostatic ArH...pi interactions retained and strengthened by the highly, but not fully, fluorinated aromatic rings.
Zheng
Hong
H
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467-3801, USA.
Comeforo
Kristofer
K
Gao
Jianmin
J
D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry*; D008840:Microfilament Proteins / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
D006845:Hydrocarbons, Fluorinated; D008840:Microfilament Proteins; C026615:villin; D010649:Phenylalanine