NDLI: Amino acid side chain induced selectivity in the hydrolysis of peptides catalyzed by a Zr(IV)-substituted Wells

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Vanhaecht, Stef Absillis, Gregory Parac-vogt, Tatjana N.
Description	Author Affiliation: Vanhaecht S ( KU Leuven, Department of Chemistry, Celestijnenlaan 200F, B-3001 Leuven, Belgium. tatjana.vogt@chem.kuleuven.be.)
Abstract	In this paper the reactivity of $K_{15}H[Zr(α_{2}-P_{2}W_{17}O_{61})_{2}]·25H_{2}O$ (1), a Zr(IV)-substituted Wells–Dawson polyoxometalate, is examined towards a series of Gly–Aa, Aa–Gly or Aa–Ser dipeptides, in which the nature and the size of the Aa amino acid side chain were varied. The rate of peptide bond hydrolysis, determined by $^{1}H$ NMR experiments, in Gly–Aa dipeptides is strongly dependent on the molecular volume and the chemical structure of the Aa side chain. When the volume of the aliphatic side chain of the Aa residue in Gly–Aa increased, a clear decrease in the hydrolysis rate was observed. Replacing one α-H in the C-terminal Gly residue of Gly–Gly by a methyl group (Gly–Ala) resulted in a 6-fold reactivity decrease, pointing towards the importance of steric factors for efficient peptide bond hydrolysis. The rate constants for peptide bond hydrolysis in Gly–Aa dipeptides at pD 5.0 and 60 °C ranged from 208.0 ± 15.6 × $10^{−6}$ $min^{−1}$ for Gly–Ser to 5.0 ± 1.0 × $10^{−6}$ $min^{−1}$ for Gly–Glu, reflecting the influence of the different nature of the amino acid side chains on the hydrolysis rate. Faster hydrolysis was observed for peptides containing Ser and Thr since the hydroxyl group in their side chain is able to facilitate amide bond hydrolysis by promoting an N→O acyl rearrangement. Peptides containing positively charged side chains at pD 5.0 show enhanced hydrolysis rates as a result of the secondary electrostatic interactions with the negatively charged surface of the polyoxometalate, which stabilize the peptide–polyoxometalate complex. A slow hydrolysis rate was observed for Gly–Glu, because of the preferential coordination of the carboxylate group in the side chain of Glu to Zr(IV), which prevents coordination of the peptide carbonyl group and its activation towards hydrolysis.
ISSN	14779226
Issue Number	43
Volume Number	42
e-ISSN	13645447
Journal	Dalton Trans.
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2013-11-21
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Amino Acids Chemistry Peptides Metabolism Tungsten Compounds Zirconium Amino Acid Sequence Catalysis Hydrogen-Ion Concentration Hydrolysis Kinetics Magnetic Resonance Spectroscopy Journal Article Research Support, Non-U.S. Gov't
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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