Conserved Protein-Polymer Interactions across Structurally Diverse Polymers Underlie Alterations to Protein Thermal Unfolding.
Conserved Protein-Polymer Interactions across Structurally Diverse Polymers Underlie Alterations to Protein Thermal Unfolding.
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DOI：
10.1021/acscentsci.2c01522
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发表时间：
2023-04-26
影响因子：
18.2
通讯作者：
Eddy, Matthew T.
中科院分区：
文献类型：
--
作者：
Pritzlaff, Amanda;Ferre, Guillaume;Dargassies, Elia;Williams, Crystal O.;Gonzalez, Daniel D.;Eddy, Matthew T.
蛋白质-聚合物缀合物广泛用于许多临床和工业应用中，但是缺乏将蛋白质-聚合物相互作用与改善的蛋白质稳定性相关的实验数据妨碍了它们的合理设计。合成化学的进步扩大了聚合物设计的调色板，包括非线性结构的开发，新型单体化学支架和疏水性的控制，但需要更多的实验数据将化学的进步转化为下一代共轭物。使用一个综合的生物物理方法，我们研究了基于聚合物的热稳定的人半乳糖凝集素蛋白质，Gal 3C，共轭聚合物的线性和非线性架构，不同程度的聚合，和不同的疏水性的分子基础。独立地改变聚合度和聚合物结构使得能够描绘有助于改善蛋白质稳定性的特定聚合物性质。从聚合物缀合的Gal 3C骨架的NMR光谱的见解揭示了热稳定的缀合物的线性和非线性聚合物架构之间共享的蛋白质-聚合物相互作用的模式。尽管聚合物化学支架存在很大差异，但导致热稳定的蛋白质-聚合物相互作用似乎是保守的。我们观察到一个明确的聚合物长度和蛋白质聚合物的热稳定性之间的关系，化学不同的聚合物共享。我们的数据表明，广泛的聚合物可用于工程共轭性质，并提供共轭设计标准。综合生物物理数据显示，类似的蛋白质-聚合物相互作用是改善蛋白质热稳定性的基础，为设计具有改善性质的缀合物提供了蓝图。
Protein–polymer conjugates are widely used in many clinical and industrial applications, but lack of experimental data relating protein–polymer interactions to improved protein stability prevents their rational design. Advances in synthetic chemistry have expanded the palette of polymer designs, including development of nonlinear architectures, novel monomer chemical scaffolds, and control of hydrophobicity, but more experimental data are needed to transform advances in chemistry into next generation conjugates. Using an integrative biophysical approach, we investigated the molecular basis for polymer-based thermal stabilization of a human galectin protein, Gal3C, conjugated with polymers of linear and nonlinear architectures, different degrees of polymerization, and varying hydrophobicities. Independently varying the degree of polymerization and polymer architecture enabled delineation of specific polymer properties contributing to improved protein stability. Insights from NMR spectroscopy of the polymer-conjugated Gal3C backbone revealed patterns of protein–polymer interactions shared between linear and nonlinear polymer architectures for thermally stabilized conjugates. Despite large differences in polymer chemical scaffolds, protein–polymer interactions resulting in thermal stabilization appear conserved. We observed a clear relation between polymer length and protein–polymer thermal stability shared among chemically different polymers. Our data indicate a wide range of polymers may be useful for engineering conjugate properties and provide conjugate design criteria. Integrative biophysical data reveal similar protein−polymer interactions underlie improved protein thermal stability, providing a blueprint to design conjugates with improved properties.
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影响因子：
8.4
作者：
Nasseri, Rasool;Tam, Kam C.
通讯作者：
Tam, Kam C.
影响因子：
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影响因子：
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通讯作者：
Roffler, Steve R.
影响因子：
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