Unprecedented Acceleration of Zirconium(IV)-Assisted Peptide Hydrolysis at Neutral pH

Abstract

4,13-Diaza-18-crown-6 substantially increases the rate of zirconium(IV) hydrolysis of unactivated peptide amide bonds under near-physiological conditions of temperature and pH. In the presence of this azacrown ether, ZrCl(4) efficiently hydrolyses both neutral and negatively charged peptides (pH 7.0-7.3, 37-60 degrees C).

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

“…The acceleration factor ranges from 2.3 for Zr(IV)-substituted Lindqvist type polyoxymetalates (Zr(IV)-Ld POMs) to 36 for Ce(IV)-substituted Keggin type polyoxymetalates (Ce(IV)-Kg POMs) [18][19][20]23,24,[27][28][29]31,32]. For Ser-Gly the intermolecular attack of the hydroxyl group on the carbonyl carbon would require the formation of an unfavorable four-membered ring.…”

“…Although the azacrown ether increased the Zr(IV) precipitation, the hydrolysis was accelerated. The application of Tris decreased the amount of Zr(IV) precipitate, but the hydrolysis rate also decreased [24].…”

“…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 ).…”

“…After 20 h at pH 6.9-7.4 and 60 • C, the hydrolysis degree ranged from 4% for Gly-Met to 42% for Gly-Gly [24]. The conversion degree increased dramatically after the addition of an azacrown ether, 4,13-diaza-18-crown-6.…”

A “Turn-On” Fluorescent Chemosensor Based on Peptidase for Detecting Copper(II)

“…Many metal ions and metal complexes are found to promote or catalyze the hydrolysis of peptide bonds in short peptides. [10][11][12][13][14][15] Bal's group identified the specific Ni(II)-related hydrolysis of peptide bonds preceding Ser/Thr-Xaa-His sequences. [16][17][18] In previous studies, the specific Cu(II)-related hydrolysis was demonstrated for peptide bonds preceding Ser-His and Thr-His sequences at elevated temperatures and pH values.…”