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i-bodies, Human Single Domain Antibodies That Antagonize Chemokine Receptor CXCR4.
Griffiths, Katherine; Dolezal, Olan; Cao, Benjamin; Nilsson, Susan K; See, Heng B; Pfleger, Kevin D G; Roche, Michael; Gorry, Paul R; Pow, Andrew; Viduka, Katerina; Lim, Kevin; Lu, Bernadine G C; Chang, Denison H C; Murray-Rust, Thomas; Kvansakul, Marc; Perugini, Matthew A; Dogovski, Con; Doerflinger, Marcel; Zhang, Yuan; Parisi, Kathy; Casey, Joanne L; Nuttall, Stewart D; Foley, Michael.
Afiliación
  • Griffiths K; From AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria 3083.
  • Dolezal O; Biomedical Manufacturing, CSIRO Manufacturing, 343 Royal Parade, Parkville, Victoria 3052.
  • Cao B; the Australian Regenerative Medicine Institute, Monash University, Wellington Road, Clayton, Victoria 3800,; Biomedical Manufacturing, CSIRO Manufacturing, Bayview Avenue, Clayton, Victoria 3168.
  • Nilsson SK; the Australian Regenerative Medicine Institute, Monash University, Wellington Road, Clayton, Victoria 3800,; Biomedical Manufacturing, CSIRO Manufacturing, Bayview Avenue, Clayton, Victoria 3168.
  • See HB; the Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009,; the Centre for Medical Research, University of Western Australia, Crawley, Western Australia 6009.
  • Pfleger KDG; the Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009,; the Centre for Medical Research, University of Western Australia, Crawley, Western Australia 6009,; Dimerix Bioscience Ltd., Nedlands, Western Australia 6009.
  • Roche M; the Doherty Institute for Infection and Immunity, University of Melbourne, 792 Elizabeth Street, Melbourne, Victoria 3000,; the Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004.
  • Gorry PR; the School of Health and Biomedical Sciences, College of Science, Engineering and Health, RMIT University, Melbourne, Victoria 3001.
  • Pow A; From AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria 3083.
  • Viduka K; From AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria 3083.
  • Lim K; From AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria 3083.
  • Lu BGC; From AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria 3083.
  • Chang DHC; From AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria 3083.
  • Murray-Rust T; From AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria 3083.
  • Kvansakul M; the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, and.
  • Perugini MA; the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, and.
  • Dogovski C; the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, and.
  • Doerflinger M; From AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria 3083.
  • Zhang Y; the Department of Medicine, St. Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia.
  • Parisi K; From AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria 3083,; the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, and.
  • Casey JL; From AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria 3083.
  • Nuttall SD; Biomedical Manufacturing, CSIRO Manufacturing, 343 Royal Parade, Parkville, Victoria 3052.
  • Foley M; From AdAlta Pty. Ltd., 15/2 Park Dr., Bundoora, Victoria 3083,; the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, and. Electronic address: m.foley@latrobe.edu.au.
J Biol Chem ; 291(24): 12641-12657, 2016 Jun 10.
Article en En | MEDLINE | ID: mdl-27036939
ABSTRACT
CXCR4 is a G protein-coupled receptor with excellent potential as a therapeutic target for a range of clinical conditions, including stem cell mobilization, cancer prognosis and treatment, fibrosis therapy, and HIV infection. We report here the development of a fully human single-domain antibody-like scaffold termed an "i-body," the engineering of which produces an i-body library possessing a long complementarity determining region binding loop, and the isolation and characterization of a panel of i-bodies with activity against human CXCR4. The CXCR4-specific i-bodies show antagonistic activity in a range of in vitro and in vivo assays, including inhibition of HIV infection, cell migration, and leukocyte recruitment but, importantly, not the mobilization of hematopoietic stem cells. Epitope mapping of the three CXCR4 i-bodies AM3-114, AM4-272, and AM3-523 revealed binding deep in the binding pocket of the receptor.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores CXCR4 / Anticuerpos de Dominio Único Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2016 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores CXCR4 / Anticuerpos de Dominio Único Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2016 Tipo del documento: Article