دورية أكاديمية
Monodisperse 130 kDa and 260 kDa Recombinant Human Hemoglobin Polymers as Scaffolds for Protein Engineering of Hemoglobin-Based Oxygen Carriers
العنوان: | Monodisperse 130 kDa and 260 kDa Recombinant Human Hemoglobin Polymers as Scaffolds for Protein Engineering of Hemoglobin-Based Oxygen Carriers |
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المؤلفون: | Jacqueline F. Aitken, Spencer J. Anthony-Cahill, Douglas D. Lemon, Michael P. Doyle, David A. Marquardt, Jeffrey S. Davidson, Janet K. Epp |
المصدر: | Journal of Functional Biomaterials, Vol 3, Iss 1, Pp 61-78 (2012) |
بيانات النشر: | MDPI AG, 2012. |
سنة النشر: | 2012 |
المجموعة: | LCC:Biotechnology LCC:Medicine (General) |
مصطلحات موضوعية: | polyhemoglobin, dihemoglobin, tetrahemoglobin, hemoglobin engineering, extravasation, pressor response, Biotechnology, TP248.13-248.65, Medicine (General), R5-920 |
الوصف: | A recombinant 130 kDa dihemoglobin which is made up of a single-chain tetra-α globin and four β globins has been expressed as a soluble protein in E. coli. The sequence of the single chain tetra-α is: αI-Gly-αII-(SerGlyGly)5Ser-αIII-Gly-αIV. This dihemoglobin has been purified and characterized in vitro by size exclusion chromatography, electrospray mass spectroscopy, equilibrium oxygen binding, and analytical ultracentrifugation. The observed values of P50 and nmax for the dihemoglobin are slightly lower than those observed for the recombinant hemoglobin rHb1.1 (a “monohemoglobin” comprised of two β globins and an αI-Gly-αII diα-globin chain). Titration of the deoxy form of dihemoglobin with CO shows that all eight heme centers bind ligand. In vivo, dihemoglobin showed increased circulating halflife and a reduced pressor response in conscious rats when compared to rHb1.1. These observations suggest that dihemoglobin is an oxygen carrying molecule with desirable in vivo properties and provides a platform for an isooncotic hemoglobin solution derived solely from a recombinant source. A 260 kDa tetrahemoglobin has also been produced by chemical crosslinking of a dihemoglobin that contains a Lys16Cys mutation in the C-terminal α-globin subunit. Tetrahemoglobin also shows reduced vasoactivity in conscious rats that is comparable to that observed for dihemoglobin. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2079-4983 |
Relation: | http://www.mdpi.com/2079-4983/3/1/61/; https://doaj.org/toc/2079-4983 |
DOI: | 10.3390/jfb3010061 |
URL الوصول: | https://doaj.org/article/b6b0f95ce22843058a5eaa16856d7271 |
رقم الأكسشن: | edsdoj.b6b0f95ce22843058a5eaa16856d7271 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 20794983 |
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DOI: | 10.3390/jfb3010061 |