Shorter Arginine homologues to stabilize peptides towards tryptic digestion

Petra Henklein, Thomas Bruckdorfer

Chemistry Today 2008; 26(6):12-15.

Abstract: Trypsin digests peptides at the position of arginine. Because shorter homologues of arginine with appropriate protecting groups for conventional Fmoc/tBu peptide synthesis are now available, three model peptides containing arginine and two shorter homologues of arginine were synthesized. They were incubated with trypsin in order to explore how stable the corresponding peptides are towards enzymatic degradation. It could be demonstrated that a peptide gains significant stability if arginine is being exchanged by a homologue containing one methylene group less. If arginine is substituted by a homologue with two methylene groups less the model peptide was almost fully stable over 24h towards enzymatic degradation.