Structural,functional and physiochemical properties of dextran-bovine hemoglobin conjugate as a hemoglobin-based oxygen carrier |
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| Affiliation: | 1. Institute of Transfusion Medicine, Academy of Military Medical Sciences, Beijing 100850, China;2. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China;3. Department of Biochemical Engineering, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, Hebei 066004, China;1. State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116023, China;2. Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;3. Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China;1. Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan;2. Center for Disease Biology and Integrative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;3. Department of Environmental and Energy Chemistry, Kogakuin University, 2665-1 Nakano-machi, Hachioji-shi, Tokyo 192-0015, Japan;4. Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan;1. Laboratory for Characterization and Processing of Polymers (LCPP), Faculty of Mechanical Engineering, University of Maribor, Smetanova ulica 17, SI-2000, Maribor, Slovenia;2. Papiertechnische Stiftung Pirnaer Straße 37, D-01809, Heidenau, Germany;3. Center of Excellence for Polysaccharide Research, Institute for Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University of Jena, Humboldtstraße 10, D-07743, Jena, Germany;4. ZMF - Center for Medical Research, Stiftingtalstraße 24, A-8010, Graz, Austria;5. National Institute of Chemistry, Department of Polymer Chemistry and Technology, Hajdrihova 19, SI-1000, Ljubljana, Slovenia;6. Institute of Paper, Pulp and Fibre Technology (IPZ), Graz University of Technology, Inffeldgasse 23, A – 8010, Graz, Austria;1. INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France;2. Université de Strasbourg, Faculté de Chirurgie-dentaire, 8 rue Sainte-Elisabeth, 67000 Strasbourg, France;3. Hemarina SA, Aéropôle centre, 29600 Morlaix, France;4. Pôle de médecine et chirurgie bucco-dentaire, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France;1. Research Center for Analytical Sciences, College of Sciences, Northeastern University, Box 332, Shenyang 110819, China;2. College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China;3. Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300071, China;1. School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea;2. Division of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea;3. College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea;4. College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 15588, Republic of Korea |
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| Abstract: | As a hemoglobin (Hb)-based oxygen carrier (HBOC), Hb suffers from the disadvantages of short half-life, renal toxicity and vasoactivity. Because dextran is a macromolecule that can be easily derivatized with various chemical moieties, conjugation of Hb with dextran can effectively increase the size of Hb and overcome the disadvantages of Hb. Thus, a dextran-bovine Hb (bHb) conjugate (dex-bHb) was prepared by conjugation of bHb with periodate-oxidized dextran here. As an important functional amino acid residue of bHb, Cys-93(β) was reversibly protected by 4,4′-dithiodipyridine to avoid reaction with periodate-oxidized dextran. Dex-bHb showed significantly higher hydrodynamic volume and higher viscosity than bHb. Conjugation with dextran stabilized the R state of bHb and slightly altered the heme environment of bHb. Conjugation with dextran decreased the P50 of bHb, lowered the sensitivity to the allosteric effectors and slightly decreased the autoxidation rate of bHb. Thus, dex-bHb was expected to act as a potent HBOC with low oxidative toxicity. |
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| Keywords: | Hemoglobin-based oxygen carriers Dextran Bovine hemoglobin Conjugation Oxygen affinity |
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