ORGN 43 |
| S-5,5,5,5',5',5'-Hexafluoroleucine (Hfl) enhances the stability of helical proteins over the native Leu-containing proteins due to the “fluoro-stabilization” effect. Herein, we report the helix propensity of Hfl, Qfl (S-5,5,5',5'-tetrafluoroleucine), Tab (S-2-amino-4,4,4-trifluoro-butyric acid), and Pff (S-pentafluorophenylalanine) to investigate the effect of introducing fluorines on helix formation energetics. Hfl and Qfl were synthesized by a chemoenzymatic stereoselective synthesis using phenylalanine dehydrogenase mediated reductive amination. Monomeric helical alanine-based peptides each containing a fluoro-amino acid or corresponding hydrocarbon amino acid at the guest position were synthesized and investigated. The helix propensity of the amino acids were calculated from the circular dichroism data based on modified Lifson-Roig theory. The helix propensity is consistently lower for the fluoro-amino acids compared to their corresponding hydrocarbon amino acid. In particular, the helix propensity for Hfl is significantly lower than Leu, implying that the fluoro-stabilization effect is much larger than previously envisioned. |
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Biologically-Related Molecules and Processes
1:00 PM-5:00 PM, Sunday, March 25, 2007 McCormick Place Lakeside -- Room E350, Level 3, Oral
Division of Organic Chemistry |