Biochemical modifications of avidin improve pharmacokinetics and biodistribution, and reduce immunogenicity
| العنوان: | Biochemical modifications of avidin improve pharmacokinetics and biodistribution, and reduce immunogenicity |
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| المؤلفون: | Francesco M. Veronese, Paolo Caliceti, G. Paganelli, Marco Chinol, E. S. Omodeo, Antonio G. Siccardi, Silvana Canevari, F. Chiolerio, Patrizia Casalini, E. Nardone, Marta Cremonesi, M. Maggiolo |
| المصدر: | British Journal of Cancer Scopus-Elsevier |
| بيانات النشر: | Nature Publishing Group|1, 1998. |
| سنة النشر: | 1998 |
| مصطلحات موضوعية: | Streptavidin, Cancer Research, Biodistribution, Biotin binding, Polyethylene Glycols, chemistry.chemical_compound, Succinylation, Mice, stomatognathic system, Animals, Tissue Distribution, Pretargeting, Mice, Inbred BALB C, biology, Chemistry, Immunogenicity, respiratory system, Avidin, Recombinant Proteins, Oncology, Biochemistry, biology.protein, PEGylation, Female, Research Article, Half-Life |
| الوصف: | Pretargeting techniques using the avidin-biotin system have shown encouraging results in both diagnostic and therapeutic clinical trials. It has been shown that in cancer therapy the ideal agent to be used for pretargeting should have a plasma half-life longer than avidin and lower immunogenicity than streptavidin in order for these procedures to be applied safely and repeatedly in patients. We prepared a recombinant form of avidin with no carbohydrates and avidins, biochemically modified either by decreasing the positive charges with succinic anhydride or by linking polyethylene glycol (PEG) at three different molar ratios and evaluated their in vivo behaviour after i.p. administration in mice. The succinylation and PEGylation of avidin increased the plasma half-life proportionally to the degree of protein modification. The procedures, however, affected the biotin binding to some extent. The biodistribution studies showed that, for all six time points (ranging from 20 min to 18 h post-injection), the liver and kidney to blood ratios were lower for PEGylated avidins than native, recombinant and succinyl avidin. Recombinant and low PEGylated avidin evoked an immune response in all mice after at least three injections. Native, recombinant and succinyl avidins showed higher serum titres than PEGylated avidins. In conclusion, the conjugation of avidin to PEG chains (n = 7) originates a compound with a suitable blood clearance, low immunogenicity and concurrent low cross-reactivity with avidin. |
| اللغة: | English |
| تدمد: | 1532-1827 0007-0920 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bed4e1f0bd4862e3b7bbcb9423245629Test http://europepmc.org/articles/PMC2062912Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bed4e1f0bd4862e3b7bbcb9423245629 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15321827 00070920 |
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