Post-Translational Modification Mimicry for Programmable Assembly of Elastin-Based Protein Polymers,ACS Macro Letters

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Post-Translational Modification Mimicry for Programmable Assembly of Elastin-Based Protein Polymers
ACS Macro Letters ( IF 5.1 ) Pub Date : 2020-02-21 , DOI: 10.1021/acsmacrolett.0c00041
Dieter M Scheibel ₁ , Md Shahadat Hossain ₁ , Amy L Smith ₁ , Christopher J Lynch ₁ , Davoud Mozhdehi ₁

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Post-translational modification (PTM) of protein polymers is emerging as a powerful bioinspired strategy to create protein-based hybrid materials with molecularly encoded assembly and function for applications in nanobiotechnology and medicine. While these modifications can be accomplished by harnessing native biological machinery (i.e., enzymes), the evolutionarily programmed specificity of these enzymes (recognition of select substrates and the limited repertoire of ligation chemistries catalyzed by these enzymes) can limit the type and linkage of PTMs appended to proteins. One approach to overcome this limitation is to leverage advances in site-selective biomolecular modification to prepare synthetic mimics of naturally occurring PTMs that are absent in nature. As a proof of concept, we used scalable bio-orthogonal reactions to prepare synthetic mimics of lipidated proteins with tunable assembly and disassembly. Additionally, we demonstrated that our PTM mimicry regulates the stimuli-responsive phase behavior of intrinsically disordered biopolymers, modulates their self-assembly at the nanoscale, and can be used for programmable disassembly of these materials in acidic environments. Synthetic PTM mimicry opens a path to encode new assembly and disassembly capabilities into hybrid materials that cannot be produced via biosynthesis.

中文翻译：

用于弹性蛋白基蛋白质聚合物可编程组装的翻译后修饰模拟

蛋白质聚合物的翻译后修饰 (PTM) 正在成为一种强大的仿生策略，可用于创建具有分子编码组装和功能的蛋白质基杂化材料，用于纳米生物技术和医学中的应用。虽然这些修饰可以通过利用天然生物机制（即酶）来完成，但这些酶的进化程序特异性（识别选择的底物和由这些酶催化的有限的连接化学组成）可以限制附加的 PTM 的类型和连接到蛋白质。克服这一限制的一种方法是利用位点选择性生物分子修饰的进步来制备自然界中不存在的天然存在的 PTM 的合成模拟物。作为概念证明，我们使用可扩展的生物正交反应来制备具有可调组装和拆卸的脂化蛋白质的合成模拟物。此外，我们证明了我们的 PTM 模拟可调节本质上无序的生物聚合物的刺激响应相行为，在纳米尺度上调节它们的自组装，并可用于这些材料在酸性环境中的可编程分解。合成 PTM 模拟开辟了一条将新的组装和拆卸能力编码为无法通过生物合成生产的混合材料的途径。并可用于在酸性环境中对这些材料进行可编程拆卸。合成 PTM 模拟开辟了一条将新的组装和拆卸能力编码为无法通过生物合成生产的混合材料的途径。并可用于在酸性环境中对这些材料进行可编程拆卸。合成 PTM 模拟开辟了一条将新的组装和拆卸能力编码为无法通过生物合成生产的混合材料的途径。

更新日期：2020-02-23

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