{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:54:40Z","timestamp":1790794480516,"version":"4.1.0"},"reference-count":42,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"40","funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["25ZR1402555"],"award-info":[{"award-number":["25ZR1402555"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22507130"],"award-info":[{"award-number":["22507130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007156","name":"Innovation and Technology Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017291","name":"Zhongshan Science and Technology Bureau","doi-asserted-by":"publisher","award":["CXTD2024006"],"award-info":[{"award-number":["CXTD2024006"]}],"id":[{"id":"10.13039\/501100017291","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Grants Council of Hong Kong","award":["17312022"],"award-info":[{"award-number":["17312022"]}]},{"name":"Research Grants Council of Hong Kong","award":["17303424"],"award-info":[{"award-number":["17303424"]}]},{"name":"Research Grants Council of Hong Kong","award":["T11-104\/22-R"],"award-info":[{"award-number":["T11-104\/22-R"]}]},{"name":"Research Grants Council of Hong Kong","award":["SRFS2324-7S01"],"award-info":[{"award-number":["SRFS2324-7S01"]}]},{"name":"Morningside"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:p>\n                    Chemical protein synthesis has transformed the preparation of homogeneous peptides and proteins with site-specific modifications. Serine\/threonine ligation offers a practical route to access difficult peptides and proteins via its aggregation-breaking intermediate, yet the preparation and regeneration of the prerequisite peptidyl salicylaldehyde ester still require the development of more efficient chemistry. Here, we report a silver(I)-mediated amide-to-ester transformation on unprotected peptides, enabled by an easily introduced\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">S<\/jats:italic>\n                    -benzylidene thioacetal scaffold. This method can chemoselectively convert backbone amides into salicylaldehyde esters in aqueous acetic acid without detectable epimerization, which is demonstrated by comprehensive syntheses of various peptide examples, the efficient total synthesis of mirror-image histones histone 2A (H2A), H2B, H3, and H4, and detailed mechanistic studies. This strategy establishes a general organic platform for programmable amide activation at the peptide or protein level.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aej5227","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:58:26Z","timestamp":1790791106000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Silver(I)-mediated amide-to-ester transformation on unprotected peptides for protein chemical synthesis and engineering"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0877-9015","authenticated-orcid":true,"given":"Zhenquan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Yin","family":"Yau","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, P. R. China."},{"name":"University of Chinese Academy of Sciences, Beijing 100049, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3976-3357","authenticated-orcid":true,"given":"Huajie","family":"Kang","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, P. R. China."},{"name":"University of Chinese Academy of Sciences, Beijing 100049, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4070-8337","authenticated-orcid":true,"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9340-9908","authenticated-orcid":true,"given":"Zhibo","family":"Han","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1437-7689","authenticated-orcid":true,"given":"Hongxiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, P. R. China."},{"name":"University of Chinese Academy of Sciences, Beijing 100049, P. R. China."},{"name":"School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5465-7727","authenticated-orcid":true,"given":"Xuechen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China."},{"name":"Materials Innovation Institute for Life Sciences and Energy (MILES), HKU-SIRI, Shenzhen, Guangdong 518000, P. R. China."},{"name":"Shanghai\u2013Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01082"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.4c00642"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2023.10.020"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00897a025"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7973629"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200503991"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1221012110"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5CS00680E"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00162"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202003652"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c05350"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202310624"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1039\/D2SC05660G"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202403396"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c17340"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-73342-3"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c11459"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6c09239"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202214053"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b04238"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)89595-7"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1039\/c39890000283"},{"key":"e_1_3_2_24_2","unstructured":"A. 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