Catalytic Hydrolysis of Peptides by Cerium(IV)

Abstract

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.

Metal assisted peptide bond hydrolysis: Chemistry, biotechnology and toxicological implications

“…The preference to cleave the N-terminal over the C-terminal peptide bond was also observed for the hydrolysis of Gly-Gly-Gly and Gly-Gly-Gly-Gly by Ce(NH 4 ) 2 (NO 3 ) 6 , as well as for the hydrolysis of Gly-Gly-Phe and Phe-Gly-Gly by Ce(IV) and ␥-cyclodextrin [23,25]. It is a consequence of the formation of a favorable fivemembered ring including the N-terminal amino group and the corresponding carbonyl group.…”

“…It is a reaction much slower than those observed for Ce(IV) salts [23]. The decrease in rate constant after incorporation of Ce(IV) into the POM structure may result from a lower number of available coordination sites, decrease in Lewis acidity, changes in the coordination environment, and a lower ligand exchange capacity.…”

“…Ce(IV) did not promote this cyclization reaction in contrast to other tested metals, e.g., Zr(IV), and Hf(IV) [23]. In the a study building on the results described above, Kassai and Grant used 17 ligands to enhance the Zr(IV)-assisted peptide bond hydrolysis, including macrocyclic crown ligands, but also HEPES and Tris and their derivatives.…”

“…However, at neutral pH the Ce(IV) and Zr(IV) compounds usually yield insoluble hydroxide species forming gels and precipitates upon dissolution. Despite of the heterogeneous nature of such solid state compounds, Komiyama and Grant groups tested their ability to hydrolyze dipeptides by adding Ce(IV) or Zr(IV) salts to their solutions [23,24]. Ce(NH 4 ) 2 (NO 3 ) 6 was the most effective hydrolytic agent among the studied precursors (Ce(NH 4 ) 2 (SO 4 ) 4 , Ce(SO 4 ) 2 , and Ce(OH) 4 ).…”

“…Such dependence was not observed for Gly-Xaa dipeptides. The Ce(IV) ion complexed to the peptides via the amino group, the carboxylate oxygen, and the carbonyl oxygen [23]. The decrease in the extent of Ce(IV) precipitation was achieved by the cyclodextrin application.…”