J. Am. Chem. Soc. 2006, 128, 15556-15557
DOI: 10.1021/ja0640445 Read in JACS
Highly fluorinated amino acids have been used to stabilize helical proteins for potential application in various protein-based biotechnologies. To gain further insight into the effect of these highly fluorinated amino acids on helix formation exclusively, we measured the helix propensity of three highly fluorinated amino acids: (S)-5,5,5,5‘,5‘,5‘-hexafluoroleucine (Hfl), (S)-2-amino-4,4,4-trifluorobutyric acid (Atb), and (S)-pentafluorophenylalanine (Pff). We have developed a short chemoenzymatic synthesis of Hfl with extremely high enantioselectivity (>99%). To measure the helix propensity (w) of the amino acids, alanine-based peptides were synthesized, purified, and investigated by circular dichroism spectroscopy (CD). On the basis of the CD data, the helix propensity of hydrocarbon amino acids can decrease up to 24-fold (1.72 kcal·mol-1·residue-1) upon fluorination. This difference in helix propensity has previously been overlooked in estimating the magnitude of the fluoro-stabilization effect (which has been estimated to be 0.32−0.83 kcal·mol-1·residue-1 for Hfl), resulting in a gross underestimation. Therefore, the full potential of the fluoro-stabilization effect should provide even more stable proteins than the fluoro-stabilized proteins to date.
Methods Mol. Biol. 2006, 340, 95-109
DOI: 110.1021/bi700701z Read in Methods Mol. Biol.
beta-Peptides have been used as a platform for developing bioactive compounds with various types of bioactivity such as antimicrobial activity, cholesterol absorption inhibition, somatostatin receptor agonist, and hDM2 inhibition. These bioactive beta-peptides have been designed based on bioactive alpha-peptides. Three main strategies have been used to design bioactive beta-peptides: direct conversion of alpha-peptide sequences into beta-peptide sequences, placement of side chains to provide desirable distribution of physicochemical properties, and the grafting of proteinaceous side chains critical for bioactivity onto beta-peptide structures. This chapter briefly discusses the various strategies employed to design bioactive beta-peptides, followed by protocols for the synthesis of N-alpha-fluorenylmethyloxycarbonyl (Fmoc)-protected beta3-amino acids from Fmoc-protected alpha-amino acids, and synthesis of beta-peptides by solid phase methods using Fmoc-based chemistry.