Origin of Proteolytic Stability of Peptide-Brush Polymers as Globular Proteomimetics.
Origin of Proteolytic Stability of Peptide-Brush Polymers as Globular Proteomimetics.
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DOI：
10.1021/acscentsci.1c01149
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发表时间：
2021-12-22
影响因子：
18.2
通讯作者：
Gianneschi NC
中科院分区：
文献类型：
--
作者：
Sun H;Qiao B;Choi W;Hampu N;McCallum NC;Thompson MP;Oktawiec J;Weigand S;Ebrahim OM;de la Cruz MO;Gianneschi NC
肽刷聚合物（PBP）代表一类新的蛋白质模拟物，其中聚合物的每个侧链是肽，其具有异常高的蛋白水解抗性，同时保持生物活性。在这里，我们试图确定这种行为的起源，并通过理论和实验相结合的方法来评估其普遍性。制备了一系列具有不同聚合物骨架结构的PBP，并对其蛋白水解稳定性和生物活性进行了研究。我们发现，聚合物骨架的疏水性的增加预示着侧链肽的蛋白水解稳定性的升高。计算机模拟，再加上小角X射线散射（SAXS）分析，揭示了这些聚合物的球状形态，其中悬垂肽冷凝周围的疏水性合成聚合物主链的疏水效应驱动。随着聚合物主链的疏水性增加，肽切割位点的溶剂暴露程度降低，降低了它们对蛋白水解酶的可及性。这项研究提供了深入了解的重要因素驱动PBP水相结构表现为球状，合成聚合物为基础的蛋白质模拟物。这项研究揭示了肽刷聚合物作为球状蛋白质模拟物和蛋白质样聚合物的起源，通过检查它们的结构和稳定性。
Peptide-brush polymers (PBPs), wherein every side-chain of the polymers is peptidic, represent a new class of proteomimetic with unusually high proteolytic resistance while maintaining bioactivity. Here, we sought to determine the origin of this behavior and to assess its generality via a combined theory and experimental approach. A series of PBPs with various polymer backbone structures were prepared and examined for their proteolytic stability and bioactivity. We discovered that an increase in the hydrophobicity of the polymer backbones is predictive of an elevation in proteolytic stability of the side-chain peptides. Computer simulations, together with small-angle X-ray scattering (SAXS) analysis, revealed globular morphologies for these polymers, in which pendant peptides condense around hydrophobic synthetic polymer backbones driven by the hydrophobic effect. As the hydrophobicity of the polymer backbones increases, the extent of solvent exposure of peptide cleavage sites decreases, reducing their accessibility to proteolytic enzymes. This study provides insight into the important factors driving PBP aqueous-phase structures to behave as globular, synthetic polymer-based proteomimetics. This study sheds light on the origin of peptide-brush polymers as globular proteomimetics and protein-like polymers by examining them for their structure and stability.
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影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
DOI：
10.1073/pnas.1312197110
发表时间：
2013-10-01
影响因子：
11.1
作者：
Cieslewicz, Maryelise;Tang, Jingjing;Pun, Suzie H.
通讯作者：
Pun, Suzie H.
影响因子：
5.5
作者：
de Jong, Djurre H.;Singh, Gurpreet;Marrink, Siewert J.
通讯作者：
Marrink, Siewert J.
影响因子：
5.5
作者：
Hilburg, Shayna L.;Ruan, Zhiyuan;Alexander-Katz, Alfredo
通讯作者：
Alexander-Katz, Alfredo
影响因子：
3
作者：
EISENHABER, F;LIJNZAAD, P;SCHARF, M
通讯作者：
SCHARF, M