Conformationally Regulated Molecular Binding and Release of Molecularly Imprinted Polypeptide Hydrogels That Undergo Helix-Coil Transition
Conformationally Regulated Molecular Binding and Release of Molecularly Imprinted Polypeptide Hydrogels That Undergo Helix-Coil Transition
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DOI：
10.1021/acs.macromol.6b02688
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发表时间：
2017-03-14
期刊：
影响因子：
5.5
通讯作者：
Miyata, Takashi
中科院分区：
文献类型：
--
作者：
Matsumoto, Kazuya;Kawamura, Akifumi;Miyata, Takashi
多肽具有固有的二级结构，例如α-螺旋、β-折叠和无规卷曲结构，这取决于它们的氨基酸序列。 β-环糊精 (CD) 作为分子识别位点的配体被引入聚赖氨酸 (PLL) 中，聚赖氨酸 (PLL) 会响应 pH 变化而发生结构转变。通过分子印迹策略设计了具有双酚 A (BPA) 动态分子识别位点的 CD 引入的 PLL (CD-PLL) 水凝胶，其中 BPA 用作模板分子，并带有微量交联剂。由此产生的具有随机线圈结构的 BPA 印迹 CD-PLL 水凝胶随着目标 BPA 的变化而发生体积变化，因为配体 CD 与 BPA 形成了复合物。此外，pH 值的变化引起 CD-PLL 链从无规卷曲到 a 螺旋的结构转变，随后 BPA 印迹的 CD-PLL 水凝胶内的分子识别位点发生构象变化。因此，BPA 印迹 CD-PLL 水凝胶中的 BPA 吸附很大程度上取决于 pH 值。 BPA 印迹 CD-PLL 水凝胶的分子识别能力由 PLL 链的螺旋线圈转变控制。 BPA 作为模型药物，通过分子印迹将 BPA 加载到 CD-PLL 水凝胶网络中，并且 BPA 模板并未从水凝胶网络中提取。负载药物的CD-PLL水凝胶中的药物释放受到PLL链的pH响应性结构转变的调节，这可以控制药物和CD配体之间的包合物的稳定性。具有动态分子识别位点的 BPA 印迹 CD-PLL 水凝胶的迷人特性表明，受蛋白质变构效应的启发，它们具有作为合适药物载体的潜力。
Polypeptides have inherent secondary structures, such as alpha-helix,) beta-sheet, and random coil structures, depending on their amino acid sequence. beta-Cyclodextrins (CDs) as ligands of molecular recognition sites were introduced into poly(Llysine) (PLL), which undergoes a structural transition in response to a pH change. CD-introduced PLL (CD-PLL) hydrogels with dynamic molecular recognition sites for bisphenol A (BPA) were strategically designed by molecular imprinting, where BPA was used as a template molecule with a minute amount of cross-linkers. The resulting BPA-imprinted CD-PLL hydrogels with a random coil structure underwent a change in volume in response to the target BPA because the ligand CDs formed a complex with BPA. Additionally, a change in pH induced a structural transition of the CD-PLL chains from the random coil to an a-helix, followed by a conformational change of the molecular recognition sites within the BPA-imprinted CD-PLL hydrogels. As a result, BPA adsorption into the BPA-imprinted CD-PLL hydrogels strongly depended on pH. The molecular recognition ability of the BPA-imprinted CD-PLL hydrogels was controlled by the helix coil transition of the PLL chains. BPA, as a model drug, was loaded within the CD-PLL hydrogel networks by molecular imprinting, and the BPA template was not extracted from the hydrogel networks. The drug release from the drug-loaded CD-PLL hydrogel was regulated by the pH-responsive structural transition of the PLL chains, which could control the stability of the inclusion complex between the drugs and CD ligands. The fascinating properties of the BPA-imprinted CD-PLL hydrogels with dynamic molecular recognition sites suggest that they exhibit potential as suitable drug carriers inspired from the allosteric effects of proteins.