Conjugate of an IgG Binding Domain with Botulinum Neurotoxin A Lacking the Acceptor Moiety Targets Its SNARE Protease into TrkA-Expressing Cells When Coupled to Anti-TrkA IgG or Fc-βNGF
| Autor: | Jiafu Wang, J. Oliver Dolly, Marc Nugent, Tomas H. Zurawski, Joan A. Geoghegan, Gary W. Lawrence |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Biomedical Engineering Pharmaceutical Science Bioengineering Immunoglobulin G law.invention 03 medical and health sciences Drug Delivery Systems law Nerve Growth Factor medicine Binding site Botulinum Toxins Type A Receptor trkA Receptor Pharmacology Vaccines Protease Binding Sites biology Chemistry Organic Chemistry Immunoglobulin Fc Fragments Fragment crystallizable region 030104 developmental biology Biochemistry IgG binding biology.protein Recombinant DNA SNARE Proteins Biotechnology |
| Zdroj: | Bioconjugate chemistry. 28(6) |
| ISSN: | 1520-4812 |
| Popis: | Numerous naturally occurring toxins can perturb biological systems when they invade susceptible cells. Coupling of pertinent targeting ligands to the active domains of such proteins provides a strategy for directing these to particular cellular populations implicated in disease. A novel approach described herein involved fusion of one mutated immunoglobulin G (IgG) binding moiety of staphylococcal protein A to the SNARE protease and translocation domain of botulinum neurotoxin A (BoNT/A). This chimera could be monovalently coupled to IgG or via its Fc region to recombinant targeting ligands. The utility of the resulting conjugates is demonstrated by the delivery of a SNARE protease into a cell line expressing tropomyosin receptor kinase A (TrkA) through coupling to anti-TrkA IgG or a fusion of Fc and nerve-growth factor. Thus, this is a versitile and innovative technology for conjugating toxins to diverse ligands for retargeted cell delivery of potential therapeutics. |
| Databáze: | OpenAIRE |
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