Peptides are often attached to polymer materials, as bioactive components, for the control of interactions between the material and its surrounding proteins and cells. However, synthesizing peptides and attaching them to polymers can be challenging and laborious. Herein, we describe the grafting of oligopeptides to an aliphatic polyester, using a one-step chemo-enzymatic synthesis with papain as the biocatalyst. To enable enzyme-mediated functionalization of the polyester, ethyl hept-6-enoylalaninate (grafter) was synthesized and attached to polylactide chains using thiol–ene click reactions. The oligopeptides were grafted onto the polylactide chains using two different synthetic routes: the grafting from strategy, in which the grafter was attached to the polyester prior to oligopeptide synthesis, or the grafting to strategy, in which oligopeptides were synthesized on the grafter first, then attached to the polymer chain. The final products were analyzed and their structures were confirmed using nuclear magnetic resonance (NMR). The peptide attachment was evaluated using size exclusion chromatography (SEC), contact angle measurement and energy-dispersive X-ray spectroscopy-scanning electron microscopy (EDS-SEM). Furthermore, the mechanistic aspects of the synthesis of the oligopeptides on the grafter were studied using molecular dynamics (MD) simulations. The simulation revealed that hydrogen bonding (between the P1 amide nitrogen of the grafter backbone and the carbonyl oxygen of D158 in the papain) maintain the grafter in a productive conformation to stabilize the transition state of nitrogen inversion, a key step of the biocatalytic mechanism. Apart from being biologically relevant, both experimental and computational results suggest that the designed grafter is a good template for initiating chemo-enzymatic synthesis. The results also showed that the grafting to strategy was more successful compared to the grafting from strategy. Overall, a successful synthesis of predefined peptide functionalized polylactide was prepared, where the oligopeptides were grafted in an easy, time efficient, and environmentally friendly way.

中文翻译：

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模板辅助酶法从聚丙交酯链合成寡肽

肽通常作为生物活性成分附着在聚合物材料上，以控制该材料与其周围的蛋白质和细胞之间的相互作用。然而，合成肽并将其连接到聚合物上可能是艰巨且费力的。在本文中，我们描述了使用木瓜蛋白酶作为生物催化剂的一步化学酶促合成方法，将寡肽接枝到脂肪族聚酯上。为了使酶能介导聚酯的功能化，合成了庚6烯丙基丙氨酸乙酯（接枝物），并使用硫醇-烯点击反应将其连接到聚丙交酯链上。使用两种不同的合成途径将寡肽接枝到聚丙交酯链上：策略接枝，其中在寡肽合成之前将接枝剂连接到聚酯上，或者接枝至策略，其中寡肽首先在接枝器上合成，然后连接到聚合物链上。分析最终产物，并使用核磁共振（NMR）确认其结构。使用尺寸排阻色谱法（SEC），接触角测量和能量分散X射线光谱法-扫描电子显微镜（EDS-SEM）评估肽的附着。此外，使用分子动力学（MD）模拟研究了嫁接机上寡肽合成的机理。该模拟显示，氢键（接枝主链的P1酰胺氮与木瓜蛋白酶中D158的羰基氧之间）使接枝器保持生产状态，以稳定氮转化的过渡态，这是生物催化机制的关键步骤。除了生物学上的相关性之外，实验和计算结果均表明，设计的接枝器是引发化学酶促合成的良好模板。结果还表明，与策略嫁接相比，策略嫁接更为成功。总体而言，已成功制备了预定义的肽官能化聚丙交酯，并以一种简单，省时且环保的方式接枝了寡肽。