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Effect of Chain-End Chemistries on the Efficiency of Coupling Antibodies to Polymers Using Unnatural Amino Acids.
Macromolecular Rapid Communications ( IF 4.2 ) Pub Date : 2020-09-16 , DOI: 10.1002/marc.202000294 Amal J Sivaram 1 , Andri Wardiana 1 , S S Hema Preethi 1 , Adrian V Fuchs 1 , Christopher B Howard 1 , Nicholas L Fletcher 1 , Craig A Bell 1 , Kristofer J Thurecht 1
Macromolecular Rapid Communications ( IF 4.2 ) Pub Date : 2020-09-16 , DOI: 10.1002/marc.202000294 Amal J Sivaram 1 , Andri Wardiana 1 , S S Hema Preethi 1 , Adrian V Fuchs 1 , Christopher B Howard 1 , Nicholas L Fletcher 1 , Craig A Bell 1 , Kristofer J Thurecht 1
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Novel conjugates that incorporate strategies for increasing the therapeutic payload, such as targeted polymeric delivery vehicles, have great potential in overcoming limitations of conventional antibody therapies that often exhibit immunogenicity and limited drug loading. Click chemistry has significantly expanded the toolbox of effective strategies for developing hybrid polymer‐biomolecule conjugates, however, effective systems require orthogonality between the polymer and biomolecule chemistries to achieve efficient coupling. Here, three cycloaddition‐based strategies for antibody conjugation to polymeric carriers are explored and show that a purely radical‐based method for polymer synthesis and subsequent biomolecule attachment has a trade‐off between coupling efficiency of the antibody and the ability to synthesize polymers with controlled chemical properties. It is shown that careful consideration of both coupling chemistries as well as the potential effect of how this modulates the chemical properties of the polymer nanocarrier should be considered during the development of such systems. The strategies described offer insight into improving conjugate development for therapeutic and theranostic applications. In this system, polymerization using conventional and established reversible addition fragmentation chain transfer (RAFT) agents, followed by multiple post‐modification steps, always leads to systems with more defined chemical architectures compared to strategies that utilize alkyne‐functional RAFT agents.
中文翻译：
链端化学对使用非天然氨基酸将抗体偶联至聚合物的效率的影响。
结合了用于增加治疗有效载荷的策略的新型缀合物（例如靶向聚合物递送载体）在克服通常表现出免疫原性和有限药物载量的常规抗体疗法的局限性方面具有巨大潜力。Click chemistry大大扩展了开发杂交聚合物-生物分子共轭物的有效策略的工具箱，但是，有效的系统要求聚合物和生物分子化学之间的正交性才能实现有效的偶联。这里，探索了三种基于环加成的抗体偶联至聚合物载体的策略，结果表明，基于自由基的聚合物合成和随后的生物分子附着方法在抗体的偶联效率与化学性质可控的聚合物合成能力之间进行权衡。结果表明，在开发这类系统时，应仔细考虑两种偶联化学以及其如何调节聚合物纳米载体化学性质的潜在影响。所描述的策略为改进用于治疗和治疗学应用的共轭物开发提供了见识。在该系统中，使用常规和已建立的可逆加成断裂链转移（RAFT）试剂进行聚合，
更新日期：2020-11-06
中文翻译：
链端化学对使用非天然氨基酸将抗体偶联至聚合物的效率的影响。
结合了用于增加治疗有效载荷的策略的新型缀合物（例如靶向聚合物递送载体）在克服通常表现出免疫原性和有限药物载量的常规抗体疗法的局限性方面具有巨大潜力。Click chemistry大大扩展了开发杂交聚合物-生物分子共轭物的有效策略的工具箱，但是，有效的系统要求聚合物和生物分子化学之间的正交性才能实现有效的偶联。这里，探索了三种基于环加成的抗体偶联至聚合物载体的策略，结果表明，基于自由基的聚合物合成和随后的生物分子附着方法在抗体的偶联效率与化学性质可控的聚合物合成能力之间进行权衡。结果表明，在开发这类系统时，应仔细考虑两种偶联化学以及其如何调节聚合物纳米载体化学性质的潜在影响。所描述的策略为改进用于治疗和治疗学应用的共轭物开发提供了见识。在该系统中，使用常规和已建立的可逆加成断裂链转移（RAFT）试剂进行聚合，
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