Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.
Biotechnol Lett. 2010 May;32(5):609-22. doi: 10.1007/s10529-010-0214-z. Epub 2010 Feb 4.
With the advent of antibody fragments and alternative binding scaffolds, that are devoid of Fc-regions, strategies to increase the half-life of small proteins are becoming increasingly important. Currently, the established method is chemical PEGylation, but more elaborate approaches are being described such as polysialylation, amino acid polymers and albumin-binding derivatives. This article reviews the main strategies for pharmacokinetic enhancement, primarily chemical conjugates and recombinant fusions that increase apparent molecular weight or hydrodynamic radius or interact with serum albumin which itself has a long plasma half-life. We highlight the key chemical linkage methods that preserve antibody function and retain stability and look forward to the next generation of technologies which promise to make better quality pharmaceuticals with lower side effects. Although restricted to antibodies, all of the approaches covered can be applied to other biotherapeutics.
随着抗体片段和缺乏 Fc 区域的其他结合支架的出现，增加小蛋白半衰期的策略变得越来越重要。目前，已确立的方法是化学 PEGylation，但更精细的方法正在被描述，如多糖唾液酸化、氨基酸聚合物和白蛋白结合衍生物。本文综述了主要的药代动力学增强策略，主要是化学缀合物和重组融合物，这些方法可以增加表观分子量或流体力学半径，或与半衰期长的血清白蛋白相互作用。我们强调了保持抗体功能和稳定性的关键化学连接方法，并期待下一代技术能够制造出质量更好、副作用更低的药物。虽然仅限于抗体，但所涵盖的所有方法都可以应用于其他生物疗法。
