Chemoenzymatic routes to enantiomerically pure 2-azatyrosine and 2-, 3- and 4-pyridylalanine derivatives
Enantiomerically pure 2-, 3- or 4-pyridylalanine (pya) and 2-azatyrosine (azatyr) are known to present various biological activities. After incorporation into appropriate peptide sequences, these heterocyclic non natural α-amino acids could behave as new substrates or inhibitors of elastase from Pseudomonas aeruginosa. This enzyme is known to be involved in nosocomial infections and infections related to the cystic fibrosis disease. New efficient chemoenzymatic preparations of those compounds using α-chymotrypsin (α-CT) are presented. Springer-Verlag 2011.
Synthesis of low-hemolytic antimicrobial dehydropeptides based on gramicidin S
The synthesis and biological activity of a novel cyclic β-sheet-type antimicrobial dehydropeptide based on gramicidin S (GS) is described. The GS analogue, containing two (Z)-(β-3-pyridyl)-α,β-dehydroalanine (ΔZ3Pal) residues at the 4 and 4′ positions (2), was synthesized by solution-phase methodologies using Boc-Leu-ΔZ3Pal azlactone. Analogue 2 exhibited high antimicrobial activity against Gram-positive bacteria and had much lower hemolytic activity than wild-type GS and the corresponding (Z)-α,β-dehydrophenylalanine (ΔZ-Phe) analogue (1).