Chemoselective Modification of Viral Proteins Bearing Metabolically Introduced "Clickable" Amino Acids and Sugars
Chemoselective Modification of Viral Proteins Bearing Metabolically Introduced "Clickable" Amino Acids and Sugars
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DOI：
10.1007/978-1-61779-151-2_5
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Carrico, Isaac S.
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文献类型：
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作者：
Banerjee, Partha S.;Carrico, Isaac S.
以真正的位点特异性方式对蛋白质进行化学修饰的固有困难往往由于需要在复杂的生物环境中工作而变得更加复杂。为了减轻这种并发症，靶标可以用非天然残留物进行代谢“预标记”，从而允许进行高度选择性的生物正交反应。叠氮化物由于其体积小，在生物合成途径中允许并且具有高特异性的反应，提供了很好的生物正交处理。这两步标记过程正在成为一种非常有效的方法来修饰治疗性蛋白质。在本章中，我们进一步采用这一策略，并应用化学选择性结扎来重塑腺病毒的表面。尽管涉及这些复杂的哺乳动物病毒的大量临床试验正在进行中，但为了推动下一代治疗方法的发展，需要对其进行简单、灵活的表面修饰的新方法。在这里，我们展示了通过基于铜辅助“点击”化学的直接化学选择方案在腺病毒表面修饰叠氮化物。这种方法在不牺牲传染性的情况下提供了广泛的效应功能。
The inherent difficulty of performing chemical modifications of proteins in a truly site-specific fashion is often compounded by the need to work within complex biological settings. In order to alleviate this complication, targets can be "prelabeled" metabolically with unnatural residues, which allow access to highly selective bioorthogonal reactions. Due to their small size, permissibility within biosynthetic pathways and access to reactions with high specificity, azides provide excellent bioorthogonal handles. This two-step labeling process is emerging as a highly effective means to modify therapeutic proteins. In this chapter, we take this strategy a step further and apply chemoselective ligation to remodel the surfaces of adenoviruses. Despite the large number of ongoing clinical trials involving these complex mammalian viruses, new methods for their facile, flexible surface modification are necessary to drive the development of next-generation therapeutics. Here we demonstrate the modification of azides on adenoviral surfaces via a straightforward chemoselective protocol based on copper-assisted "click" chemistry. This method provides access to a wide array of effector functionalities without sacrificing infectivity.