Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

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

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

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