{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362825893506456576.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1158/1535-7163.mct-13-0358"}},{"identifier":{"@type":"URI","@value":"https://aacrjournals.org/mct/article-pdf/12/10/2273/2323561/2273.pdf"}}],"dc:title":[{"@value":"Receptor-Directed Chimeric Toxins Created by Sortase-Mediated Protein Fusion"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n                  <jats:p>Chimeric protein toxins that act selectively on cells expressing a designated receptor may serve as investigational probes and/or antitumor agents. Here, we report use of the enzyme sortase A (SrtA) to create four chimeric toxins designed to selectively kill cells bearing the tumor marker HER2. We first expressed and purified: (i) a receptor recognition-deficient form of diphtheria toxin that lacks its receptor-binding domain and (ii) a mutated, receptor-binding–deficient form of anthrax-protective antigen. Both proteins carried at the C terminus the sortase recognition sequence LPETGG and a H6 affinity tag. Each toxin protein was mixed with SrtA plus either of two HER2-recognition proteins—a single-chain antibody fragment or an Affibody—both carrying an N-terminal G5 tag. With wild-type SrtA, the fusion reaction between the toxin and receptor-recognition proteins approached completion only after several hours, whereas with an evolved form of the enzyme, SrtA*, the reaction was virtually complete within 5 minutes. The four fusion toxins were purified and shown to kill HER2-positive cells in culture with high specificity. Sortase-mediated ligation of binary combinations of diverse natively folded proteins offers a facile way to produce large sets of chimeric proteins for research and medicine. Mol Cancer Ther; 12(10); 2273–81. ©2013 AACR.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1382825893506456577","@type":"Researcher","foaf:name":[{"@value":"Andrew J. McCluskey"}],"jpcoar:affiliationName":[{"@value":"Authors' Affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825893506456576","@type":"Researcher","foaf:name":[{"@value":"R. John Collier"}],"jpcoar:affiliationName":[{"@value":"Authors' Affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"15357163"},{"@type":"EISSN","@value":"15388514"}],"prism:publicationName":[{"@value":"Molecular Cancer Therapeutics"}],"dc:publisher":[{"@value":"American Association for Cancer Research (AACR)"}],"prism:publicationDate":"2013-10-01","prism:volume":"12","prism:number":"10","prism:startingPage":"2273","prism:endingPage":"2281"},"reviewed":"false","url":[{"@id":"https://aacrjournals.org/mct/article-pdf/12/10/2273/2323561/2273.pdf"}],"createdAt":"2013-08-15","modifiedAt":"2023-07-03","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1363383444010647680","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Effect of Diphtheria Toxin-Based Gene Therapy for Hepatocellular Carcinoma"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1158/1535-7163.mct-13-0358"},{"@type":"CROSSREF","@value":"10.3390/cancers12020472_references_DOI_28YWIIzbaEpNpuoZmEkvHShyiqi"}]}