515871-93-9Relevant academic research and scientific papers
Protease-catalyzed peptide synthesis for the site-specific incorporation of α-fluoroalkyl amino acids into peptides
Thust, Sven,Koksch, Beate
, p. 2290 - 2296 (2007/10/03)
Substitution of native amino acids by fluoroalkyl analogues represents a new approach for the design of biologically active peptides with increased metabolic stability as well as defined secondary structure and provides a powerful label for spectroscopic investigations. Here, we introduce a methodology for the incorporation of sterically demanding Cα-fluoroalkyl amino acids into the P1 position of peptides catalyzed by the commercially available proteases trypsin and α-chymotrypsin. The combination of 4-guanidinophenyl ester of Cα-fluoroalkyl amino acids as substrate mimetics with frozen-state reaction conditions provided the most efficient strategy for protease-catalyzed site-specific introduction of this kind of nonnatural amino acids into peptide sequences. Consequently, a library of di-, tri-, and tetrapeptides containing α-methyl, α-difluoromethyl, and α-trifluoromethyl alanine, leucine, and phenylalanine in the P1 position was synthesized catalyzed by trypsin as well as α-chymotrypsin. Trypsin was shown to be the more versatile protease.
