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Using model peptides containing Asp or Asn, a mechanism was elucidated that involves a succinimide intermediate. Succinimides formed readily from Asn at neutral pH, whereas a higher rate of formation from Asp peptides was observed at more acidic pHs. Succinimides were found to be relatively stable in the absence of nucleophiles. Since racemization of Asp residues, as well as deamidation of Asn, involves a succinimide intermediate, sites of d-Asp and isoAsp in LLPs should also be considered as potential sites of protein covalent cross-linking.<\/jats:p>","DOI":"10.1042\/bcj20180529","type":"journal-article","created":{"date-parts":[[2018,9,4]],"date-time":"2018-09-04T16:05:26Z","timestamp":1536077126000},"page":"3189-3200","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Spontaneous cross-linking of proteins at aspartate and asparagine residues is mediated via a succinimide intermediate"],"prefix":"10.1042","volume":"475","author":[{"given":"Michael G.","family":"Friedrich","sequence":"first","affiliation":[{"name":"Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin L.","family":"Schey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J. 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