Computational study on nonenzymatic peptide bond cleavage at asparagine and aspartic acid

The Journal of Physical Chemistry. a
Saron CatakManuel F Ruiz-López

Abstract

Nonenzymatic peptide bond cleavage at asparagine (Asn) and glutamine (Gln) residues has been observed during peptide deamidation experiments; cleavage has also been reported at aspartic acid (Asp) and glutamic acid (Glu) residues. Although peptide backbone cleavage at Asn is known to be slower than deamidation, fragmentation products are often observed during peptide deamidation experiments. In this study, mechanisms leading to the cleavage of the carboxyl-side peptide bond of Asn and Asp residues were investigated using computational methods (B3LYP/6-31+G**). Single-point solvent calculations at the B3LYP/6-31++G** level were carried out in water, utilizing the integral equation formalism-polarizable continuum (IEF-PCM) model. Mechanism and energetics of peptide fragmentation at Asn were comparatively analyzed with previous calculations on deamidation of Asn. When deamidation proceeds through direct hydrolysis of the Asn side chain or through cyclic imide formationvia a tautomerization routeit exhibits lower activation barriers than peptide bond cleavage at Asn. The fundamental distinction between the mechanisms leading to deamidationvia a succinimideand backbone cleavage was found to be the difference in nucleophilic entities...Continue Reading

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Jul 11, 2006·The Journal of Physical Chemistry. a·Saron CatakManuel F Ruiz-López
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Citations

Jun 12, 2013·Journal of Molecular Modeling·Wichien Sang-aroon, Vithaya Ruangpornvisuti
Nov 19, 2013·Journal of Molecular Modeling·Wichien Sang-aroonVithaya Ruangpornvisuti
Feb 10, 2010·Pharmaceutical Research·Mark Cornell ManningDerrick S Katayama
Jun 7, 2011·Journal of Bacteriology·Jana SchirrmeisterSusanne Zehner
Apr 1, 2011·Journal of Pharmaceutical Sciences·Tim J KamerzellY John Wang
Sep 15, 2012·Chemistry : a European Journal·Asli YildirimViktorya Aviyente
Dec 20, 2011·Organic & Biomolecular Chemistry·Jon I MujikaAdrian J Mulholland
Feb 7, 2014·The Journal of Physical Chemistry. B·Mohammad A HalimRaymond A Poirier
Dec 3, 2016·Journal of Peptide Science : an Official Publication of the European Peptide Society·Kenzo Aki, Emiko Okamura
May 17, 2018·Beilstein Journal of Organic Chemistry·Andrea Angelo Pierluigi TripodiGábor Mező
Sep 13, 2019·Nature·Enrico CappelliniEske Willerslev
Dec 4, 2019·The Biochemical Journal·Michael G FriedrichRoger J W Truscott
Feb 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yi-Ting FangYung-Chuan Liu
Feb 12, 2021·Chembiochem : a European Journal of Chemical Biology·Megan A RochaRachel W Martin
Jan 20, 2009·The Journal of Physical Chemistry. a·Saron CatakManuel F Ruiz-López
Mar 31, 2009·The Journal of Physical Chemistry. B·Jon I MujikaAdrian J Mulholland
Oct 12, 2010·Journal of Agricultural and Food Chemistry·Jing ZhaoLingyun Chen
Nov 19, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Etienne VillainAndrey V Kajava

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