Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Instrumentation Center, National Taiwan University, Taipei 10617, Taiwan.
Molecules. 2023 Mar 23;28(7):2888. doi: 10.3390/molecules28072888.
Cross-strand interactions are important for the stability of β-sheet structures. Accordingly, cross-strand diagonal interactions between glutamate and arginine analogs with varying side-chain lengths were studied in a series of β-hairpin peptides. The peptides were analyzed by homonuclear two-dimensional nuclear magnetic resonance methods. The fraction folded population and folding free energy of the peptides were derived from the chemical shift data. The fraction folded population trends could be rationalized using the strand propensity of the constituting residues, which was not the case for the peptides with lysine analogs, highlighting the difference between the arginine analogs and lysine analogs. Double-mutant cycle analysis was used to derive the diagonal ion-pairing interaction energetics. The most stabilizing diagonal cross-strand interaction was between the shortest residues (i.e., Asp2-Agp9), most likely due to the least side-chain conformational penalty for ion-pair formation. The diagonal interaction energetics in this study involving the arginine analogs appears to be consistent with and extend beyond our understanding of diagonal ion-pairing interactions involving lysine analogs. The results should be useful for designing β-strand-containing molecules to affect biological processes such as amyloid formation and protein-protein interactions.
链间相互作用对于β-折叠结构的稳定性很重要。因此，本研究在一系列β发夹肽中研究了谷氨酸和具有不同侧链长度的精氨酸类似物之间的链间对角线相互作用。通过同核二维核磁共振方法对肽进行了分析。根据化学位移数据推导出肽的折叠部分种群和折叠自由能。肽的折叠部分种群趋势可以用组成残基的链倾向来合理化，而赖氨酸类似物的情况并非如此，这突出了精氨酸类似物和赖氨酸类似物之间的差异。双突变体循环分析用于推导出对角线离子对相互作用的能量学。最稳定的对角线链间相互作用是在最短的残基之间（即 Asp2-Agp9），这很可能是由于形成离子对的侧链构象惩罚最小。本研究中涉及精氨酸类似物的对角线相互作用能量学似乎与我们对涉及赖氨酸类似物的对角线离子对相互作用的理解一致，并有所扩展。这些结果对于设计包含β-链的分子以影响生物过程（如淀粉样蛋白形成和蛋白质-蛋白质相互作用）应该是有用的。
