Beilstein J. Org. Chem.2017,13, 2869–2882, doi:10.3762/bjoc.13.279
. The opposite phenomenon was observed in other cases, and this may be explained by specific interactions of fluorinated residues with the respective enzyme binding sites. Noteworthy is that 5,5,5-trifluoroisoleucine is able to significantly protect peptides from proteolysis by all enzymes included in
stability; trifluoroisoleucine; Introduction
Peptide-based drugs are promising pharmaceuticals since they offer several advantages including high selectivity, specificity, and efficacy for recognizing and binding to their targets [1][2][3][4][5][6]. However, their application as drugs is often limited due
site and the particular protease [39][40].
Here, we extend these studies to include highly fluorinated, sterically demanding HfLeu, and 5,5,5-trifluoroisoleucine (TfIle) and to investigate their effects on proteolytic stability towards the serine proteases α-chymotrypsin, elastase, and proteinase K
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Graphical Abstract
Figure 1:
(a) Structures of isoleucine (1), leucine (2), and their fluorinated analogues 5,5,5-trifluoroisole...
Beilstein J. Org. Chem.2013,9, 2009–2014, doi:10.3762/bjoc.9.236
synthesis of (2S,3S)-5,5,5-trifluoroisoleucine (L-5-F3Ile) and (2R,3S)-5,5,5-trifluoro-allo-isoleucine (D-5-F3-allo-Ile) was developed. The hydrophobicity of L-5-F3Ile was examined and it was incorporated into a model peptide via solid phase peptide synthesis to determine its α-helix propensity. The α-helix
propensity of 5-F3Ile is significantly lower than Ile, but surprisingly high when compared with 4’-F3Ile.
Keywords: amino acids; CD-spectroscopy; fluorine; helix propensity; organo-fluorine; trifluoroisoleucine; Introduction
Due to the unique physicochemical properties of fluorine, namely its small size
observed, this stability was mainly attributed to a higher hydrophobicity or the formation of a fluorous core [2][10]. Tirrell et al. found that the biological function of the helical GCN4 transcription factor can be retained, when utilizing racemic mixtures of 5,5,5-trifluoroisoleucine (5-F3Ile) as
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Graphical Abstract
Scheme 1:
Synthesis of optically active N-acyloxazolidinone 5 from 4,4,4-trifluorobutanoic acid. Conditions: ...