Beta-sheet propensity of highly fluorinated amino acids

ORGN 128

Hsien-Po Chiu and Richard P. Cheng. Department of Chemistry, SUNY Buffalo, 520 Natural Science Complex, Buffalo, NY 14260-3000
Highly fluorinated amino acids have been used to stabilize helical motifs, however minimal studies have been performed on sheet-containing proteins. In this presentation, we measured the beta-sheet propensity using the protein G B1 domain for various amino acids: pentafluorophenylalanine, 5,5,5,5',5',5'-hexafluoroleucine, 5,5,5',5'-tetrafluoroleucine, phenylalanine, leucine, alanine, and glycine. The corresponding 56-residue proteins were synthesized by solid phase peptide synthesis using Fmoc-based chemistry. Thermal denaturation of these proteins were monitored by circular dichroism spectroscopy. The denaturation of all proteins was fully reversible. Interestingly, fluorinated amino acids favor beta-sheet formation over their corresponding hydrocarbon amino acids. Furthermore, pentafluorophenylalanine was the most beta-sheet stabilizing amino acid. These results suggest that highly fluorinated amino acids may be useful for stabilizing beta-sheet-containing proteins.