{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:03:25Z","timestamp":1789380205385,"version":"build-2803163510"},"reference-count":71,"publisher":"Wiley","issue":"38","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20524"],"award-info":[{"award-number":["U23A20524"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22271126"],"award-info":[{"award-number":["22271126"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["224B2703"],"award-info":[{"award-number":["224B2703"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"publisher","award":["25JRRA726"],"award-info":[{"award-number":["25JRRA726"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["lzujbky\u20102025\u2010it30"],"award-info":[{"award-number":["lzujbky\u20102025\u2010it30"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2026,9,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Site\u2010selective Cys bioconjugation is central to chemical biology and therapeutic development. Owing to the widespread availability of amine\u2010containing building blocks, the modular assembly of alkylamines and Cys holds significant promise for diverse applications. However, existing strategies often suffer from reversible linkages, stereochemical heterogeneity, or limited modularity. Here we report a programmable pyridine\u2010based chemoselective sequential conjugation platform that integrates a thianthrenium leaving group and a fluorine handle on a single pyridine scaffold, enabling sequential, orthogonal coupling of alkylamines and Cys to form non\u2010chiral, stable aryl\u2010Cys linkages. The reaction exhibits exceptional functional group compatibility and high chemoselectivity in both the alkylamine\u2010 and thiol\u2010conjugation steps. The platform supports late\u2010stage peptide diversification and stapling, protein functionalization, and streamlined construction of a HER2\u2010targeting ADC (MRG002) analog with a tunable drug\u2010to\u2010antibody ratio. The resulting ADC shows slightly enhanced cytotoxicity in HER2\u2010positive cells, comparable activity in antigen\u2010negative controls, and markedly improved payload retention in human serum.<\/jats:p>","DOI":"10.1002\/anie.3286230","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T10:48:19Z","timestamp":1783507699000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modular Assembly of Bioconjugates Enabled by a Pyridine\u2010Based Chemoselective Sequential Conjugation Platform"],"prefix":"10.1002","volume":"65","author":[{"given":"Xiaobo","family":"Dang","sequence":"first","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Shang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongtao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9238-6582","authenticated-orcid":false,"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoqing","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CC02268G"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.3c00534"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200801313"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5740"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500399p"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6OB00808A"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C1CC11114K"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4CS00393D"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00253"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CS00354A"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2393"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914067107"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.017"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201038039\u2010x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo502136n"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2015.11.015"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201035795\u20108"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161\u20105890(00)00105\u2010X"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2415"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.2c00915"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010025\u201001704\u20103"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.03.042"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912\u2010025\u201001713\u2010y"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202201843"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2023.102306"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2OB02262A"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.8b00252"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201803174"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201703572"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2968"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.116"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4CS00102H"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557\u2010018\u20100021\u2010z"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4QO02268H"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CS00048C"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202500262"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201500667"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1cc14164c"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2108"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201904193"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0910589"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15739"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b00172"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b04115"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c12170"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7SC04292B"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c10185"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202315748"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c08936"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201806009"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202001287"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201712589"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2413"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b08831"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c02721"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.3c00322"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.2c00419"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c10334"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c11864"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx3003998"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.052183"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201047188\u20106"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201611051"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201051217\u20109"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557\u2010023\u201001388\u20107"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c10259"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202300318"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbe.3c00123"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.4c00422"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202410616"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c03413"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.3286230","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.3286230","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.3286230","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:09:22Z","timestamp":1789376962000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.3286230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":71,"journal-issue":{"issue":"38","published-print":{"date-parts":[[2026,9,14]]}},"alternative-id":["10.1002\/anie.3286230"],"URL":"https:\/\/doi.org\/10.1002\/anie.3286230","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"assertion":[{"value":"2026-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e3286230"}}