Disulfide bond bridged divalent antibody-toxin, (Fab-PE38fl)(2), with the toxin PE38 fused to the light
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Won, JaeSeon | - |
dc.contributor.author | Choe, MuHyeon | - |
dc.date.accessioned | 2021-09-09T05:34:30Z | - |
dc.date.available | 2021-09-09T05:34:30Z | - |
dc.date.created | 2021-06-10 | - |
dc.date.issued | 2008-08 | - |
dc.identifier.issn | 1017-7825 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/122919 | - |
dc.description.abstract | B3 antibody specifically binds the Lewis(Y)-related carbohydrate antigen of man), carcinomas, and it is used as a model antibody in this study. In a previous study, the Fab fragment of the antibody was fused to a 38 kDa truncated form of Pseudomonas exotoxin A, PE38, to make Fab-PE38, where PE38 is fused to the Fd fragment of the Fab domain. This parent monomer molecule, Fab-PE38, had no cysteine in the hinge region, and it could not make a disulfide bond to form a disulfide bond bridged homodimer [7]. In this study, we constructed three different kinds of divalent Fab-toxin fusion homodimers where the toxin is fused to the light chain of Fab, (Fab-PE38fl)(2). In addition to the PE38 toxin fused to the light chain, these three molecules have different hinge sequences h1, h2, and h3 making Fabh1-, Fabh2-, and Fabh3-PE38fl monomers, respectively. These hinges contain only one cysteine on different positions of the hinge sequence. The disulfide bond between the hinge region of two monomers forms homodimers (Fabh1-PE38fl)(2), (Fabh2-PE38fl)(2), and (Fabh3-PE38fl)(2). The refolding yields of these dimers were 516-fold higher than a previously constructed dimer where the PE38 was fused to the Fd fragment (Fabh1-PE38)(2) [8]. Our data suggest that the steric repulsion between the two PE38s in (Fabh1-PE38)(2) during disulfide bridge formation is relieved by fusing it at the end of the light chain. The best cytotoxicity value of these dimers; showed about 2.5-fold higher on an MCF7 cell line than that of the monovalent reference molecule in ng/ml scale, which is 15-fold higher in pM scale. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY | - |
dc.subject | SINGLE-CHAIN IMMUNOTOXINS | - |
dc.subject | RECOMBINANT IMMUNOTOXIN | - |
dc.subject | PSEUDOMONAS EXOTOXIN | - |
dc.subject | ANTITUMOR-ACTIVITY | - |
dc.subject | ESCHERICHIA-COLI | - |
dc.subject | FV IMMUNOTOXINS | - |
dc.subject | HUMAN CARCINOMA | - |
dc.subject | FAB | - |
dc.subject | FRAGMENT | - |
dc.subject | MICE | - |
dc.title | Disulfide bond bridged divalent antibody-toxin, (Fab-PE38fl)(2), with the toxin PE38 fused to the light | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choe, MuHyeon | - |
dc.identifier.scopusid | 2-s2.0-56749176169 | - |
dc.identifier.wosid | 000258787500019 | - |
dc.identifier.bibliographicCitation | JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, v.18, no.8, pp.1475 - 1481 | - |
dc.relation.isPartOf | JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY | - |
dc.citation.title | JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY | - |
dc.citation.volume | 18 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | 1475 | - |
dc.citation.endPage | 1481 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.identifier.kciid | ART001275407 | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
dc.relation.journalResearchArea | Biotechnology & Applied Microbiology | - |
dc.relation.journalResearchArea | Microbiology | - |
dc.relation.journalWebOfScienceCategory | Biotechnology & Applied Microbiology | - |
dc.relation.journalWebOfScienceCategory | Microbiology | - |
dc.subject.keywordPlus | SINGLE-CHAIN IMMUNOTOXINS | - |
dc.subject.keywordPlus | RECOMBINANT IMMUNOTOXIN | - |
dc.subject.keywordPlus | PSEUDOMONAS EXOTOXIN | - |
dc.subject.keywordPlus | ANTITUMOR-ACTIVITY | - |
dc.subject.keywordPlus | ESCHERICHIA-COLI | - |
dc.subject.keywordPlus | FV IMMUNOTOXINS | - |
dc.subject.keywordPlus | HUMAN CARCINOMA | - |
dc.subject.keywordPlus | FAB | - |
dc.subject.keywordPlus | FRAGMENT | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordAuthor | antibody refolding | - |
dc.subject.keywordAuthor | light chain-toxin fusion | - |
dc.subject.keywordAuthor | divalent antibody-toxin | - |
dc.subject.keywordAuthor | homodimer | - |
dc.subject.keywordAuthor | cytotoxicity | - |
dc.subject.keywordAuthor | Pseudomonas exotoxin A | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
145 Anam-ro, Seongbuk-gu, Seoul, 02841, Korea+82-2-3290-2963
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.