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Effect of Fluoro-Amino Acids on
Protein Secondary Structure Stability
Richard Cheng, Department of Chemistry, University at Buffalo, SUNY
Buffalo, NY 14260-3000
Unfolded
Monomeric
Folded Multimeric
Fluorocarbon Protein
Stability
Hydrocarbon Protein
Stability
Energy
Protein
Helix
Helix Bundle Protein
The stability of enzymes catalysts for
application in organic synthesis can be
0.49
improved by incorporating fluorinated amino
F3C
1.15
acids. This fluoro-stabilization effect has been
attributed to hydrophobics, because the
H3N
COO
Atb
difference in hydrophobicity between Leu and
Hydrocarbon
Fluorocarbon
Hfl (0.4 kcal·mol-1·residue-1) is similar to the
Stabilization
Stabilization
change in overall helical protein stability upon
H3N
COO
substituting Leu with Hfl (0.32-0.83 kcal·molPreviously Estimated
0.32-0.83
Leu
Fluoro-Stabilization Effect
1·residue-1). This estimation of the fluoroCF3
stabilization effect assumes that the helix
F3C
propensities are the same for the two amino
H3N
COO
Hfl
acids. We aim to measure the -helix and -sheet propensities of fluoro-amino acids. This
would be useful for quantitatively predicting the effect of fluoro-amino acids on protein stability.
We have measured the helix propensity of fluoro-amino acids such as Hfl, showing that helix propensity
decreases significantly upon introducing fluorines. Our results show that Hfl is significantly less favorable
than Leu for helix formation. Therefore, the fluoro-stabilization effect is larger than the previous estimation of
0.32-0.83 kcal·mol-1·residue-1 by 1.15 kcal·mol-1·residue-1 for Hfl. These results suggest that the fluorostabilization effect more than overcomes the less favorable helix propensity. Also, the fluoro-stabilization
effect may be more than just hydrophobics, but may also include more specific interactions such as those
involving the dipole moments of the trifluoromethyl groups. Furthermore, fluoro-amino acids such as Hfl may
be more suitable in non-helical structures (i.e. -sheet) to realize the full potential of the fluoro-stabilization
effect.