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Here, a series of artificial enzymes is developed based on single\u2010chain nanoparticles (SCNPs) formed through intramolecular folding of a triblock copolypeptide, polyethylene glycol\u2010\n                    <jats:italic>b<\/jats:italic>\n                    \u2010poly(L\u2010glutamic acid)\u2010\n                    <jats:italic>b<\/jats:italic>\n                    \u2010poly(oligo(ethylene glycol)\u2010L\u2010glutamate) (PEG\n                    <jats:sub>113<\/jats:sub>\n                    \u2010\n                    <jats:italic>b<\/jats:italic>\n                    \u2010PGlu\n                    <jats:sub>112<\/jats:sub>\n                    \u2010\n                    <jats:italic>b<\/jats:italic>\n                    \u2010P(Glu\u2010EG\n                    <jats:sub>2<\/jats:sub>\n                    )\n                    <jats:sub>99<\/jats:sub>\n                    ). The central poly\u2010Glu block is intramolecularly cross\u2010linked via coordination with transition metal ions (Fe\n                    <jats:sup>2+<\/jats:sup>\n                    \/Fe\n                    <jats:sup>3+<\/jats:sup>\n                    , Mn\n                    <jats:sup>2+<\/jats:sup>\n                    , Co\n                    <jats:sup>2+<\/jats:sup>\n                    , Cu\n                    <jats:sup>2+<\/jats:sup>\n                    \/Zn\n                    <jats:sup>2+<\/jats:sup>\n                    ), mimicking the natural folding of polypeptides into proteins. Co\u2010precipitation with ammonia water generates metal\/alloy oxide nanoclusters within the cross\u2010linked polyGlu domain, providing a large surface\u2010to\u2010volume ratio. The metal oxide nanoclusters function as coenzymes. They not only facilitate a structural transition from \u03b1\u2010helices to \u03b2\u2010strands within the cross\u2010linked polyGlu domain but also demonstrate specific peroxidase (POD) or superoxide dismutase (SOD) activities, which are tailored to the specific metal species involved. The FeOx\u2010complexed artificial enzyme (Fe\u2010enzyme) is selected to exemplify its therapeutic effects of mitigating oxidative stress and inflammation in a rheumatoid arthritis mouse model. These artificial enzymes feature a soft, degradable polypeptide skeleton, tunable side\u2010chain functionalities, high enzyme\u2010like activity with minimal metal content (&lt; 5 wt.%), and secondary structures similar to natural proteins.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202502053","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T07:10:14Z","timestamp":1753341014000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Polypeptide Single\u2010Chain Nanoparticle Derived Artificial Enzyme"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0549-7836","authenticated-orcid":false,"given":"Yongjia","family":"Yang","sequence":"first","affiliation":[{"name":"Beijing Area Major Laboratory of Peptide and Small Molecular Drugs School of Pharmaceutical Sciences Capital Medical University  Beijing 100069 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