Mykhailiuk P. New fluorinated analogs of natural amino acids as 19F-NMR labels for peptide studies.

The thesis is devoted to the synthesis of new conformationally constrained and rigid trifluoromethyl-substituted analogs of natural amino acids and their applications as 19F labels for structural peptide studies by solid state 19F-NMR. New trifluoromethyl-substituted conformationally rigid L-?-amino acid was synthesized. The compound was designed as a proper 19F-label for substitution of the nonpolar natural amino acids in peptides. The library of 19F-labels - conformationally restricted trifluoromethyl-substituted L ?-amino acids - for proline substutution was designed and synthesized. New approach to the synthesis fluorinated analogs of the natural amino acids was developed. The method is based on the trifluoromethylcyclopropanation of alkenes by trifluoromethyldiazomethane over metal catalysts. The 19F-labels obtained were incorporated into antimicrobial peptides PGLa and GS. Four labelled analogs of PGLa and one labelled analog of GS were synthesized. Compatibility of the developed 19F-labels withthe criteria for a proper label was demonstrated. The synthesis of the membrane-active peptide SAP was optimized. Six labelled analogues of SAP possessing developed 19F-labels were obtained. The structure and the orientation of SAP in the model membrane were revealed by 19F-NMR analysis of fluorine labelled SAP analogs.