School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, Guangdong, China.
Key Lab of Molecular Target and Clinical Pharmacology, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, Guangdong, China.
Langmuir. 2021 Jan 26;37(3):1288-1296. doi: 10.1021/acs.langmuir.0c03351. Epub 2021 Jan 12.
A series of side-chain thioether-linked OEGylated poly(glutamic acid) (PGAs) have been synthesized by "thiol-ene" synthetic methodology, where both the oligo-ethylene glycol (OEG) length and the hydrophobic linkers at the side chains are varied to learn how these structural features affect the secondary structure and thermoresponsive behaviors in water. Before side-chain oxidation, the structural factors affecting the α-helicity include the backbone length, the OEG length, and the hydrophobic linkers' length at the side chains; however, the OEG length plays the most crucial role among these factors because longer OEG around the peripheral side chains can stop water penetration into the backbone to disturb the intramolecular H bonds, which finally allows stabilizing the α-helix; after the oxidation, the polypeptides show increased α-helicity because of the enhanced hydrophilicity. More interestingly, a rare oxidation-induced conformation transition from the ordered β-sheet to the ordered α-helix can be achieved. In addition, only the OEGylated poly(glutamic acids) (PGAs) with shorter hydrophobic linkers and longer OEG can display the thermoresponsive properties before the oxidation but the subsequent oxidation can cause the polypeptides bearing longer hydrophobic linkers to exhibit the thermosensitivity since sulfone formation at the side chain can lead to final hydrophilicity-hydrophobicity balance. This work is meaningful to understand the secondary structure-associated solution behaviors of the synthetic polypeptides.
一系列侧链硫醚连接的聚（谷氨酸）（PGAs）已通过“硫烯”合成方法合成，其中聚乙二醇（OEG）的长度和侧链上的疏水性连接物都有所变化，以了解这些结构特征如何影响二级结构和在水中的热响应行为。在侧链氧化之前，影响α螺旋构象的结构因素包括主链长度、OEG 长度和侧链上的疏水性连接物长度；然而，OEG 长度在这些因素中起着最关键的作用，因为侧链周围较长的 OEG 可以阻止水渗透到主链中干扰分子内氢键，从而最终稳定α螺旋；氧化后，由于亲水性增强，多肽显示出更高的α螺旋度。更有趣的是，还可以实现从有序β-折叠到有序α-螺旋的罕见氧化诱导构象转变。此外，只有具有较短疏水性连接物和较长 OEG 的 OEG 化聚（谷氨酸）（PGAs）在氧化前才具有热响应特性，但随后的氧化会导致具有较长疏水性连接物的多肽表现出热敏性，因为侧链上的砜形成会导致最终的亲水性-疏水性平衡。这项工作对于理解合成多肽的二级结构相关溶液行为具有重要意义。
