Summary
Metabolic stabilization of pharmacologically active peptides can be achieved by incorporation of sterically hindered non-natural amino acids, e.g. Cα,α-disubstituted amino acids.α-Trifluoromethyl substituted amino acids, a subclass of Cα,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.
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Koksch, B., Sewald, N., Burger, K. et al. Peptide modification by incorporation ofα-trifluoromethyl substituted amino acids. Amino Acids 11, 425–434 (1996). https://doi.org/10.1007/BF00807946
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DOI: https://doi.org/10.1007/BF00807946