{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:18:05Z","timestamp":1791292685808,"version":"4.1.0"},"reference-count":57,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T00:00:00Z","timestamp":1298937600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T00:00:00Z","timestamp":1298937600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Analytical Biochemistry"],"published-print":{"date-parts":[[2011,3]]},"DOI":"10.1016\/j.ab.2010.11.040","type":"journal-article","created":{"date-parts":[[2010,12,3]],"date-time":"2010-12-03T04:41:07Z","timestamp":1291351267000},"page":"234-243","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":47,"title":["Identification of isomerization and racemization of aspartate in the Asp\u2013Asp motifs of a therapeutic protein"],"prefix":"10.1016","volume":"410","author":[{"given":"Jennifer","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Yip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viswanatham","family":"Katta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ab.2010.11.040_b0005","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1021\/ja00871a030","article-title":"Co-operative effects of functional groups in peptides. I. Aspartyl-serine derivatives","volume":"84","author":"Bernhard","year":"1962","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ab.2010.11.040_b0010","series-title":"Stability of Protein Pharmaceuticals Part A: Chemical and Physical Pathways of Protein Degradation","first-page":"1","author":"Clarke","year":"1992"},{"key":"10.1016\/j.ab.2010.11.040_b0015","series-title":"Formulation Characterization, and Stability of Protein Drugs","first-page":"1","author":"Powell","year":"1996"},{"key":"10.1016\/j.ab.2010.11.040_b0020","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0021-9258(19)75855-4","article-title":"Deamidation and racemization at asparaginyl and aspartyl residues in peptides","volume":"262","author":"Geiger","year":"1987","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0025","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1023\/A:1015999012852","article-title":"Chemical pathways of peptide degradation III: effect of primary sequence on the pathways on deamidation of asparaginyl residues in hexapeptides","volume":"7","author":"Patel","year":"1990","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ab.2010.11.040_b0030","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1023\/A:1018981231468","article-title":"Chemical pathways of peptide degradation IV: pathways kinetics and mechanism of degradation of an aspartyl residue in a model hexapeptide","volume":"10","author":"Oliyai","year":"1993","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ab.2010.11.040_b0035","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1021\/bi951526c","article-title":"Isomerization of an aspartic acid residue in the complementarity-determining regions of a recombinant antibody to human IgE: identification and effect on binding affinity","volume":"35","author":"Cacia","year":"1996","journal-title":"Biochemistry"},{"key":"10.1016\/j.ab.2010.11.040_b0040","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0378-4347(00)00548-X","article-title":"Identification of multiple sources of charge heterogeneity in a recombinant antibody","volume":"752","author":"Harris","year":"2001","journal-title":"J. Chromatogr. B"},{"key":"10.1016\/j.ab.2010.11.040_b0045","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.4049\/jimmunol.171.6.2840","article-title":"A failure to repair self-proteins leads to T cell hyperproliferation and autoantibody production","volume":"171","author":"Doyle","year":"2003","journal-title":"J. Immunol."},{"key":"10.1016\/j.ab.2010.11.040_b0050","doi-asserted-by":"crossref","first-page":"32676","DOI":"10.1074\/jbc.M604847200","article-title":"Isoaspartyl posttranslational modification triggers anti-tumor T and B lymphocyte immunity","volume":"281","author":"Doyle","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0055","doi-asserted-by":"crossref","first-page":"4541","DOI":"10.4049\/jimmunol.177.7.4541","article-title":"Intracellular protein modification associated with altered T cell functions in autoimmunity","volume":"177","author":"Yang","year":"2006","journal-title":"J. Immunol."},{"key":"10.1016\/j.ab.2010.11.040_b0060","doi-asserted-by":"crossref","first-page":"26094","DOI":"10.1074\/jbc.M503624200","article-title":"Protein l-isoaspartyl methyltransferase catalyzed in vivo racemization of aspartate-25 in mammalian histone H2B","volume":"280","author":"Young","year":"2005","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0065","doi-asserted-by":"crossref","first-page":"9148","DOI":"10.1021\/ja953505b","article-title":"Accelerated racemization of aspartic acid and asparagine residues via succinimide intermediates: an ab initio theoretical exploration of mechanism","volume":"118","author":"Radkiewicz","year":"1996","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ab.2010.11.040_b0070","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1111\/j.1399-3011.1987.tb03390.x","article-title":"Propensity for spontaneous succinimide formation from aspartyl and asparaginyl residues in cellular proteins","volume":"30","author":"Clarke","year":"1987","journal-title":"Int. J. Pept. Protein Res."},{"key":"10.1016\/j.ab.2010.11.040_b0075","doi-asserted-by":"crossref","first-page":"6164","DOI":"10.1016\/S0021-9258(18)83327-0","article-title":"Succinimide formation from aspartyl and asparaginyl peptides as a model for the spontaneous degradation of proteins","volume":"264","author":"Stephenson","year":"1989","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0080","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1021\/ja0026814","article-title":"Neighboring side chain effects on asparaginyl and aspartyl degradation: an ab initio study of the relationship between peptide conformation and backbone NH acidity","volume":"123","author":"Radkiewicz","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ab.2010.11.040_b0085","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1023\/A:1018944800691","article-title":"Chemical pathways of peptide degradation. IV. Effect of the primary sequence on the pathways of degradation of aspartyl residues in model hexapeptides","volume":"11","author":"Oliyai","year":"1994","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ab.2010.11.040_b0090","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1021\/bi061500t","article-title":"Aspartate isomerization in the complementarity-determining regions of two closely related monoclonal antibodies","volume":"46","author":"Wakankar","year":"2007","journal-title":"Biochemistry"},{"key":"10.1016\/j.ab.2010.11.040_b0095","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/s11095-007-9241-4","article-title":"Accumulation of succinimide in a recombinant monoclonal antibody in mildly acidic buffers under elevated temperatures","volume":"24","author":"Chu","year":"2007","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ab.2010.11.040_b0100","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1021\/ac0617870","article-title":"18O labeling method for identification and quantification of succinimide in proteins","volume":"79","author":"Xiao","year":"2007","journal-title":"Anal. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0105","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1021\/ac702245c","article-title":"Separation and characterization of an IgG2 antibody containing a cyclic imide in CDR1 of light chain by hydrophobic interaction chromatography and mass spectrometry","volume":"80","author":"Valliere-Douglass","year":"2008","journal-title":"Anal. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0110","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1021\/ac802708s","article-title":"Direct identification and quantification of aspartyl succinimide in an IgG2 mAb by RapiGest assisted digestion","volume":"81","author":"Huang","year":"2009","journal-title":"Anal. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0115","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/j.1399-3011.1995.tb01318.x","article-title":"Effect of adjacent histidine and cysteine residues on the spontaneous degradation of asparaginyl- and aspartyl-containing peptides","volume":"45","author":"Brennan","year":"1995","journal-title":"Int. J. Pept. Protein Res."},{"key":"10.1016\/j.ab.2010.11.040_b0120","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1021\/bi7018223","article-title":"Isomerization of a single aspartyl residue of anti-epidermal growth factor receptor immunoglobulin \u03b32 antibody highlights the role avidity plays in antibody activity","volume":"47","author":"Rehder","year":"2008","journal-title":"Biochemistry"},{"key":"10.1016\/j.ab.2010.11.040_b0125","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1016\/S0021-9258(18)53460-8","article-title":"Selective deamidation of ribonuclease A. Isolation and characterization of the resulting isoaspartyl aspartyl derivatives","volume":"268","author":"Donato","year":"1993","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0130","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/pro.5560030119","article-title":"Identification of succinimide sites in proteins by N-terminal sequence analysis after alkaline hydroxylamine cleavage","volume":"3","author":"Kwong","year":"1993","journal-title":"Protein Sci."},{"key":"10.1016\/j.ab.2010.11.040_b0135","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1023\/A:1019814713428","article-title":"Characterization of asparagine deamidation and aspartate isomerization in recombinant human interleukin-11","volume":"19","author":"Zhang","year":"2002","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ab.2010.11.040_b0140","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/S0731-7085(02)00525-3","article-title":"Quantification of the isomerization of Asp residue in recombinant human alpha A-crystallin by reversed-phase HPLC","volume":"30","author":"Sadakane","year":"2003","journal-title":"J. Pharm. Biomed. Anal."},{"key":"10.1016\/j.ab.2010.11.040_b0145","doi-asserted-by":"crossref","first-page":"14262","DOI":"10.1016\/S0021-9258(18)71672-4","article-title":"Formation of isoaspartate at two distinct sites during in vitro aging of human growth hormone","volume":"264","author":"Johnson","year":"1989","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0150","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1110\/ps.041062905","article-title":"Deamidation: differentiation of aspartyl from isoaspartyl products in peptides by electron capture dissociation","volume":"14","author":"Cournoyer","year":"2005","journal-title":"Protein. Sci."},{"key":"10.1016\/j.ab.2010.11.040_b0155","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1021\/ac051691q","article-title":"Detecting deamidation products in proteins by electron capture dissociation","volume":"78","author":"Cournoyer","year":"2006","journal-title":"Anal. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0160","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jasms.2006.08.008","article-title":"Quantitating the relative abundance of isoaspartyl residues in deamidated proteins by electron capture dissociation","volume":"18","author":"Cournoyer","year":"2007","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"10.1016\/j.ab.2010.11.040_b0165","doi-asserted-by":"crossref","unstructured":"W.Y.K. Chan, T.W.D. Chan, P.B. O\u2019Connor, Electron transfer dissociation with supplemental activation to differentiate aspartic and isoaspartic residues in doubly charged peptide cations, J. Am. Soc. Mass Spectrom. doi:10.1016\/j.jasms.2010.02.002.","DOI":"10.1016\/j.jasms.2010.02.002"},{"key":"10.1016\/j.ab.2010.11.040_b0170","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1073\/pnas.69.1.274","article-title":"Glutamic acid as a precursor to N-terminal pyroglutamic acid in mouse plasmacytoma protein","volume":"69","author":"Twardzik","year":"1972","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ab.2010.11.040_b0175","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1021\/bi00702a003","article-title":"Cell-free synthesis of amino-terminal l-pyroglutamic acid","volume":"13","author":"Jones","year":"1974","journal-title":"Biochemistry"},{"key":"10.1016\/j.ab.2010.11.040_b0180","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1034\/j.1399-3011.2001.00895.x","article-title":"Stability and CTL activity of N-terminal glutamic acid containing peptides","volume":"57","author":"Beck","year":"2001","journal-title":"J. Pept. Res."},{"key":"10.1016\/j.ab.2010.11.040_b0185","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1021\/ac051827k","article-title":"Formation of pyroglutamic acid from N-terminal glutamic acid in immunoglobulin gamma antibodies","volume":"78","author":"Chelius","year":"2006","journal-title":"Anal. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0190","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0006-3002(59)90230-6","article-title":"Amino acid analog incorporation into bacterial proteins","volume":"34","author":"Cowie","year":"1959","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ab.2010.11.040_b0195","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/0006-291X(66)90408-6","article-title":"Formylation of amino acid analogues of methionine sRNA","volume":"24","author":"Trupin","year":"1966","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ab.2010.11.040_b0200","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/0003-9861(70)90170-0","article-title":"Studies on the ability of norleucine to replace methionine in the initiation of protein synthesis of E. coli","volume":"141","author":"Kerwar","year":"1970","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.ab.2010.11.040_b0205","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0021-9258(17)31291-7","article-title":"Biosynthesis and incorporation into protein of norleucine by Escherichia coli","volume":"264","author":"Bogosian","year":"1989","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0210","doi-asserted-by":"crossref","first-page":"4352","DOI":"10.1021\/bi00180a032","article-title":"Incorporation of norleucine at methionine positions in recombinant human macrophage colony stimulating factor (M-CSF, 4-153) expressed in Escherichia coli: structural analysis","volume":"33","author":"Randhawa","year":"1994","journal-title":"Biochemistry"},{"key":"10.1016\/j.ab.2010.11.040_b0215","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1002\/elps.200800157","article-title":"Application of iCIEF for characterization and quantitative analysis of recombinant protein charge heterogeneity","volume":"29","author":"Sosic","year":"2008","journal-title":"Electrophoresis"},{"key":"10.1016\/j.ab.2010.11.040_b0220","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF01321887","article-title":"Racemization of aspartic acid in the extracellular matrix proteins of primary and secondary dentin","volume":"53","author":"Saleh","year":"1993","journal-title":"Calcified Tissue Int."},{"key":"10.1016\/j.ab.2010.11.040_b0225","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/262279b0","article-title":"Aspartic acid racemisation in dentine as a measure of ageing","volume":"262","author":"Helman","year":"1976","journal-title":"Nature"},{"key":"10.1016\/j.ab.2010.11.040_b0230","doi-asserted-by":"crossref","first-page":"12538","DOI":"10.1016\/S0021-9258(18)67121-2","article-title":"Age-dependent accumulation of protein residues which can be hydrolyzed to d-aspartic acid in human erythrocytes","volume":"261","author":"Brunauer","year":"1986","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0235","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0021-9150(92)90132-Z","article-title":"On the accumulation of d-aspartate in elastin and other proteins of the ageing aorta","volume":"97","author":"Powell","year":"1992","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.ab.2010.11.040_b0240","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1016\/S0021-9258(18)53661-9","article-title":"Structural alterations in the peptide backbone of beta-amyloid core protein may account for its deposition and stability in Alzheimer\u2019s disease","volume":"268","author":"Roher","year":"1993","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ab.2010.11.040_b0245","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0047-6374(01)00363-3","article-title":"Racemization of aspartic acid in human proteins","volume":"1","author":"Ritz-Timmea","year":"2002","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.ab.2010.11.040_b0250","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2220\/biomedres.12.315","article-title":"Racemization of aspartic acids at specific sites in \u03b1A-crystallin from aged human lens","volume":"12","author":"Fujii","year":"1991","journal-title":"Biomed. Res."},{"key":"10.1016\/j.ab.2010.11.040_b0255","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jpba.2007.11.050","article-title":"Identification and quantification of degradations in the Asp\u2013Asp motifs of a recombinant monoclonal antibody","volume":"47","author":"Xiao","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"10.1016\/j.ab.2010.11.040_b0260","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1126\/science.3353715","article-title":"Tertiary structure is a principal determinant to protein deamidation","volume":"240","author":"Kossiakoff","year":"1989","journal-title":"Science"},{"key":"10.1016\/j.ab.2010.11.040_b0265","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.1021\/bi00435a058","article-title":"Calcium affects the spontaneous degradation of aspartyl\/asparaginyl residues in calmodulint","volume":"28","author":"Ota","year":"1989","journal-title":"Biochemistry"},{"key":"10.1016\/j.ab.2010.11.040_b0270","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1399-3011.1974.tb02355.x","article-title":"Sequence dependent deamidation rates for model peptides of cytochrome C","volume":"6","author":"Robinson","year":"1974","journal-title":"Int. J. Pept. Protein Res."},{"key":"10.1016\/j.ab.2010.11.040_b0275","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1126\/science.183.4120.85","article-title":"Primary sequence dependence of the deamidation of rabbit muscle aldolase","volume":"183","author":"McKerrow","year":"1974","journal-title":"Science"},{"key":"10.1016\/j.ab.2010.11.040_b0280","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1073\/pnas.69.7.1816","article-title":"Deamidation in vivo of an asparagine residue of rabbit muscle Aldolase","volume":"69","author":"Midelfort","year":"1972","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ab.2010.11.040_b0285","first-page":"3509","article-title":"Succinimide formation at Asn 55 in the complementarity determining region of a recombinant monoclonal antibody IgG1 heavy chain","volume":"98","author":"Yan","year":"2009","journal-title":"Biotechnology"}],"container-title":["Analytical Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0003269710007657?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0003269710007657?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T21:00:59Z","timestamp":1757710859000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0003269710007657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,3]]}},"alternative-id":["S0003269710007657"],"URL":"https:\/\/doi.org\/10.1016\/j.ab.2010.11.040","relation":{},"ISSN":["0003-2697"],"issn-type":[{"value":"0003-2697","type":"print"}],"subject":[],"published":{"date-parts":[[2011,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Identification of isomerization and racemization of aspartate in the Asp\u2013Asp motifs of a therapeutic protein","name":"articletitle","label":"Article Title"},{"value":"Analytical Biochemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ab.2010.11.040","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2010 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}