Stabilizing and Destabilizing Effects of Phenylalanine → F₅-Phenylalanine Mutations on the Folding of a Small Protein

Abstract

We report a systematic evaluation of phenylalanine-to-pentafluorophenylalanine (Phe --> F5-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe --> F5-Phe mutations are interesting because aryl-perfluoroaryl interactions of optimal geometry are intrinsically more favorable than aryl-aryl interactions and because perfluoroaryl units are more hydrophobic than are analogous aryl units. One mutant, Phe-10 --> F5-Phe, provides enhanced tertiary structural stability relative to the native sequence. The other six mutants analyzed caused a decrease in stability.

Organic fluorine as a polypeptide building element: in vivo expression of fluorinated peptides, proteins and proteomes

“…22 This amino acid was chosen as there are several reports regarding the effects of fluorinated saturated carbon atoms but only a few reports of the effects of aromatic amino acids and their impact on stability. In order to assay the conformational stability they performed a backbone thioester exchange because this process can be easily monitored.…”

Aromatische Ringe in chemischer und biologischer Erkennung: Energien und Strukturen

“…[138] [139] Nukleobasen wechselwirken dabei unterschiedlich mit Arenen und Perfluorarenen. [140] So bindet 9-Ethyladenin besser an einen synthetischen Rezeptor (analog zu 3 in Abbildung 3) durch Stapelungen mit einem Naphthyl-(DG = À2.49 kcal mol À1 ) als mit einem Perfluornaphthylring (DG = À1.88 kcal mol À1 ).…”

Preferred side-chain constellations at antiparallel coiled-coil interfaces

“…We have recently developed an experimental design that facilitates the rapid study of sequence-stability relationships among antiparallel coiled coils (20,(22)(23)(24). Our model system (N T -C; Fig.…”