{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:49:26Z","timestamp":1790848166417,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"30","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272145"],"award-info":[{"award-number":["82272145"]}],"id":[{"id":"10.13039\/501100001809","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":[[2025,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This work describes the rational design and synthesis of hepsin\u2010recognized amphiphilic\u2010branched peptides (\n                    <jats:bold>DMN\u2010SIPL<\/jats:bold>\n                    ) that can form solid condensates through liquid\u2013liquid phase separation (LLPS) upon enzymatic reaction. The peptide forms solid\u2010like condensates both in vitro and in living cells, triggered by type\u2010II membrane\u2010associated serine peptidase, hepsin, whose overexpression determines prostate cancer progression. Specifically, integrating self\u2010assembly, hepsin hydrolysis, and hepsin\u2010binding domain generates a branched substrate that acts as a precursor for enzyme\u2010induced LLPS. Upon binding hepsin on the cell membrane,\n                    <jats:bold>DMN\u2010SIPL<\/jats:bold>\n                    forms condensates initiated by hepsin\u2010induced self\u2010assembly. The prostate cancer cells then uptake these condensates via lipid raft\u2010mediated endocytosis. The entrapped hepsin in the condensates further hydrolyzes the\n                    <jats:bold>DMN\u2010SIPL<\/jats:bold>\n                    to stabilize the intracellular condensates. Structure\u2013activity relationship reveals the importance of enzyme\u2010binding motif, enzyme\u2010recognized motif, and the self\u2010assembly motif. Mechanistic studies indicate that the resulting solid\u2010like condensates modulate cancer cell metabolism by inhibiting hepsin upstream protein activation and downstream signal transduction, ultimately inducing cancer cell growth inhibition selectively. As a first example, this work investigates enzymatic LLPS condensate formation in living cells, paving the way to generate functional synthetic biomolecular condensates through LLPS for biomedical applications.\n                  <\/jats:p>","DOI":"10.1002\/anie.202504958","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T02:59:47Z","timestamp":1747882787000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Enzyme Induced Solid\u2010Like Condensates Formation of Engineered Peptide in Living Cells for Prostate Cancer Inhibition"],"prefix":"10.1002","volume":"64","author":[{"given":"Ying","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, Department of Chemistry, School of Science, Institute of Natural Sciences, Westlake Institute for Advanced Study Westlake University  No. 600 Dunyu Road Hangzhou Zhejiang 310024 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, Department of Chemistry, School of Science, Institute of Natural Sciences, Westlake Institute for Advanced Study Westlake University  No. 600 Dunyu Road Hangzhou Zhejiang 310024 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoting","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, Department of Chemistry, School of Science, Institute of Natural Sciences, Westlake Institute for Advanced Study Westlake University  No. 600 Dunyu Road Hangzhou Zhejiang 310024 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8796-0367","authenticated-orcid":false,"given":"Huaimin","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, Department of Chemistry, School of Science, Institute of Natural Sciences, Westlake Institute for Advanced Study Westlake University  No. 600 Dunyu Road Hangzhou Zhejiang 310024 China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, School of Life Sciences Westlake University  Hangzhou Zhejiang 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