title: Peptide modification by incorporation ofα-trifluoromethyl substituted amino acids.
abstract: Metabolic stabilization of pharmacologically active peptides can be achieved by incorporation of sterically hindered non-natural amino acids, e.g. C (α,α) -disubstituted amino acids.α-Trifluoromethyl substituted amino acids, a subclass of C (α,α) -disubstituted amino acids, also fulfil this requirement while featuring additional properties based on the electronic influence of the fluorine substituents.This review summarizes the results concerning the stability of peptides containingα-TFM amino acids towards proteolysis byα-chymotrypsin. Furthermore, configurational effects ofα-TFMAla on the proteolytic stability of peptides are explained using empirical force field calculations. The influence ofα-TFMAla incorporation on the secondary structure of selected tripeptide amides is compared to the effects exerted by its fluorine-free analogue, aminoisobutyric acid.Finally, results on metabolic stabilization and biological activity of modified thyrotropin releasing hormone are interpreted.
authors.affiliation: Department of Biochemistry, University of Leipzig, Talstraße 33, D-04103, Leipzig, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Koksch
authors.forename: N
authors.initials: N
authors.lastname: Sewald
authors.forename: K
authors.initials: K
authors.lastname: Burger
authors.forename: H D
authors.initials: HD
authors.lastname: Jakubke