作为潜在红细胞替代品的高分子量松弛和紧张四价态聚合人血红蛋白的规模化生产和生物物理特征。

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2024-11-11 Epub Date: 2024-10-30 DOI:10.1021/acs.biomac.4c01024

Mohd Asim Khan, Tanmay Salvi, Griffin J Beyer, Amna Abdalbaqi, Megan Allyn, Alejandro Bresolin, Andre F Palmer

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引用次数: 0

摘要

高分子量（HMW）（>500 kDa）戊二醛聚合人血红蛋白（PolyhHb）是一种很有前途的血红蛋白氧载体（HBOC），因为它能降低血管收缩和组织氧化损伤的风险。此前，曾在中试规模上利用切向流过滤（TFF）技术合成了高分子量（T）四元态 PolyhHb，用于去除低分子量物质。然而，由于 T 态 PolyhHb 的氧亲和力较低，因此仅限于特定的生物医学应用，这就促使人们需要在中试规模上生产高氧亲和力的弛缓（R）季态 PolyhHb。本研究探讨了高分子量 T 态和 R 态 PolyhHb 的中试规模合成和广泛的生物物理表征。结果表明，成功合成了分子量增加（1000-1500 kDa）的低氧亲和力和高氧亲和力 PolyhHb。总之，T 态和 R 态 PolyhHb 为制造具有不同氧亲和力和潜在生物医学应用的氧治疗药物提供了一个平台。

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Scalable Production and Biophysical Characterization of High-Molecular-Weight Relaxed and Tense Quaternary State Polymerized Human Hemoglobin as Potential Red Blood Cell Substitutes.

High-molecular-weight (HMW) (>500 kDa) glutaraldehyde-polymerized human hemoglobin (PolyhHb) is a promising hemoglobin-based oxygen carrier (HBOC) due to its decreased risk of vasoconstriction and oxidative tissue injury. Previously, HMW tense (T) quaternary state PolyhHb was synthesized at the pilot scale with tangential flow filtration (TFF) for the removal of low-molecular-weight species. However, T-state PolyhHb is limited to specific biomedical applications due to its low oxygen affinity, thus motivating the need to produce high oxygen affinity relaxed (R) quaternary state PolyhHb at the pilot scale. This study explored the pilot-scale synthesis and extensive biophysical characterization of both HMW T- and R-state PolyhHb. The resultant characterization demonstrated the successful synthesis of low and high oxygen affinity PolyhHb with increased molecular weight (∼1000-1500 kDa). Overall, T- and R-state PolyhHb provides a platform for manufacturing oxygen therapeutics with a diverse range of oxygen affinities and potential biomedical applications.

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.