Conformational studies peptide group interactions

Various diastereomeric di-, tri-, and tetrapeptides that carry the sterically demanding trifluoromethyl group instead of the natural a-proton at different positions within these short peptide sequences have been designed, and their stability towards enzymatic hydrolysis has been investigated. The structures of the a-trifluoromethyl (aTfm)-substituted amino acids are shown in Scheme 1. From these studies we gained valuable information on how a-trifluoromethyl-substi-tuted peptides may interact with proteins. The aTfm amino acids used in this study combine the conformational restrictions [49-52] of C -dialkylation with the unique stereoelectronic properties of the fluorine atom and have shown interesting effects on peptide-enzyme interactions [53,54]. 

Further studies of the C-peptide showed that a helix is very strongly affected by pH, due to the presence of ionizable side chains. Helical stabilization occurs when favorable interactions can occur between ionized side chains and the helix dipole, and also when ionization can promote hydrogen bonding between side chains. In the case of C-peptide, two ionized groups (with p/fas near 3.5 and 6.5) promote helix formation and helix content follows a bellshaped curve, with a maximum near pH 5. 81 Increasing concentrations of salt (NaCl) also increases conformational stability. 98 ... 

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