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A wide range of groups including trifluoromethylthio (SCF\n            <jats:sub>3<\/jats:sub>\n            ), difluoromethylthio (SCF\n            <jats:sub>2<\/jats:sub>\n            H), (ethoxycarbonyl)difluoromethylthio (SCF\n            <jats:sub>2<\/jats:sub>\n            CO\n            <jats:sub>2<\/jats:sub>\n            Et), alkylthio, and arylthio were readily incorporated. The rapid reaction kinetics of Trp modification and full tolerance with other 19 proteinogenic amino acids, as well as the super dissolving capability of TFA, render this method suitable for all kinds of Trp-containing peptides without limitations from sequences, hydrophobicity, and aggregation propensity. The late-stage modification of 15 therapeutic peptides (1.0 to 7.6 kilodaltons) and the improved bioactivity and serum stability of SCF\n            <jats:sub>3<\/jats:sub>\n            - and SCF\n            <jats:sub>2<\/jats:sub>\n            H-modified melittin analogs illustrated the effectiveness of this method and its potential in pharmacokinetic property improvement.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adp9958","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T17:59:51Z","timestamp":1720634391000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":35,"title":["Clickable tryptophan modification for late-stage diversification of native peptides"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7671-7636","authenticated-orcid":true,"given":"Yisa","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, 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 SAR, P. R. China."},{"name":"Chemistry and Chemical Engineering Guangdong Laboratory, Shantou, Guangdong Province 515063, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3341-2856","authenticated-orcid":true,"given":"Xueqian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1412-4584","authenticated-orcid":true,"given":"Han","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, 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 SAR, P. R. 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