Poly(zwitterionic)protein conjugates offer increased stability without sacrificing binding affinity or bioactivity.
Poly(zwitterionic)protein conjugates offer increased stability without sacrificing binding affinity or bioactivity.
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DOI：
10.1038/nchem.1213
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发表时间：
2011-12-11
期刊：
影响因子：
21.8
通讯作者：
中科院分区：
文献类型：
--
作者：
治疗性蛋白治疗是针对许多具有挑战性的疾病的一种有吸引力的方法。不幸的是，天然蛋白质本身在生理条件下往往不稳定，降低了生物利用度，因此增加了所需的剂量。与聚乙二醇（PEG）偶联通常用于增加稳定性，但这对生物活性有不利影响。在这里，我们介绍了与两性离子聚合物如聚羧基甜菜碱的偶联。我们发现聚（羧甜菜碱）偶联以类似聚乙二醇化的方式提高了稳定性，但由于增强的蛋白质-底物疏水相互作用，新的偶联物保留甚至提高了结合亲和力。这种化学通过避免在稳定性和亲和力之间妥协的需要，为蛋白质疗法的发展开辟了一条新的途径。
Treatment with therapeutic proteins is an attractive approach to targeting a number of challenging diseases. Unfortunately, the native proteins themselves are often unstable in physiological conditions, reducing bioavailability and therefore increasing the dose that is required. Conjugation with poly(ethylene glycol) (PEG) is often used to increase stability, but this has a detrimental effect on bioactivity. Here, we introduce conjugation with zwitterionic polymers such as poly(carboxybetaine). We show that poly(carboxybetaine) conjugation improves stability in a manner similar to PEGylation, but that the new conjugates retain or even improve the binding affinity as a result of enhanced protein–substrate hydrophobic interactions. This chemistry opens a new avenue for the development of protein therapeutics by avoiding the need to compromise between stability and affinity.
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14.8
作者：
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通讯作者：
Brocchini, Steve
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PRIME, KL;WHITESIDES, GM
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WHITESIDES, GM
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Ivanov, IA
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