Synthesis, Structural and Biological Studies of Ubiquitin Mutants Containing (2S,4S)-5-Fluoroleucine Residues Strategically Placed in the Hydrophobic Core

摘要

understanding protein folding is currently a major research challenge and multidimensional NMR spectroscopy is increasingly being employed in its solution. Although fluoroaromatic and derivatised amino acids have lond been used as reporter groups for NMR spectroscopic investigations of proteins, the first study with fluorinated aliphatic amino acids appeared only in 1996 when we reported incorporation of (2S,4S)-5-fluoroleucine (FLeu) in place of all 13 Leu residues in dihydrofolate reductase using biological methods. Since then, trifluorome-thionine and fluoroproline have been incorporated into proteins and recently synthetic and in vivo techniques were used to incorporate mixtures of diastereoisomers of 5,5,5-trifluoroleucine and 5,5,5,5~',5~',5~'-hexafluoroleucine into the leucine zipper peptide GCN4-p1.