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However, the sluggish and site\u2010nonselective generation of isoAsp residues in proteins severely impedes in\u2010depth biological investigations as well as the exploitation of its unique \u03b2\u2010linkage features. Herein, we introduce a method that allows site\u2010selective and rapid generation of isoAsp residues in proteins. This method leverages the genetic incorporation of a side\u2010chain\u2010esterified Asp derivative (BnD), which undergoes facile intramolecular arrangement to form the key intermediate, aspartyl succinimide (Suc); subsequent hydrolysis of Suc gives rise to isoAsp as the major product. On native sites of proteins, including Cu\/Zn superoxide dismutase and calmodulin, we demonstrate that BnD\u2010mediated isoAsp formation is faster than Asn deamidation generally by three orders of magnitude.<\/jats:p>","DOI":"10.1002\/anie.202500983","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T03:46:36Z","timestamp":1741751196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Site\u2010Selectively Accelerating the Generation of \u03b2\u2010Linked Residue Isoaspartate in Proteins"],"prefix":"10.1002","volume":"64","author":[{"given":"Qifan","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Synthetic Biology School of Life Sciences Faculty of Medicine Tianjin University  Tianjin 300072 China"},{"name":"State Key Laboratory and Institute of Elemento\u2010Organic Chemistry College of Chemistry Nankai University  Tianjin 300071 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