Catalytic hydrolysis of peptides by cerium(IV)

Oligopeptides are efficiently hydrolyzed by Ce(IV) to the corresponding amino acids under mild conditions. The pseudo first-order rate constants for the hydrolysis of H-Gly-Phe-OH and H-Gly-Gly-OH at pH 7.0 and 50 degrees C are 3.5 x 10(-1) and 2.8 x 10(-1) h(-1), with [Ce(NH4)2(NO3)6]0=10mM (the half-lives are 2.0 and 2.5 h). The catalytic activity of the Ce(IV) is far greater than those of other lanthanide ions and non-lanthanide ions. No oxidative cleavage was observed under the reaction conditions. Catalytic turnover of the Ce(IV) was also evidenced. The hydrolysis is fast especially when the substrates have no metal-coordinating side chains. Tripeptides and tetrapeptides are hydrolyzed at the similar rates as the dipeptides. In the hydrolysis of tripeptides, the amide linkage near the N-terminus is preferentially hydrolyzed. Neither the N-carbobenzyloxy derivative nor the amide of H-Gly-Phe-OH is hydrolyzed to a measurable extent, showing that both the terminal amino group and the carboxylate are coordinated to the Ce(IV) ion. This complexation is further confirmed by 1H NMR spectroscopy. The Ce(IV) ion is therefore one of the most active catalysts for peptide hydrolysis.