Department of Chemistry, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar 382355, India.
Department of Biological Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar 382355, India.
J Phys Chem B. 2024 Oct 24;128(42):10434-10450. doi: 10.1021/acs.jpcb.4c03336. Epub 2024 Oct 9.
The cationic peptide octaarginine (R8) is a prominent cell-penetrating peptide and has been extensively researched as a carrier of diverse cell-destined cargo. In this work, we describe the coassembly of R8 with small molecule thiazolyl benzenesulfonamide (TBS) derivatives. Physical complexation of R8 with three TBS derivatives across a range of weight ratios results in the formation of a distinctive set of nano- and microstructures. A detailed structural characterization of the R8:TBS-derivative coassemblies has been performed by a combination of FTIR, XRD, SEM, and DSC. The major functional groups that facilitate coassembly include sulfonamide SO and NH groups of the TBS derivatives, and the guanidinium of R8, via a combination of cation-π and hydrogen-bonding interactions. The R8:4F-TBS coassembly displays singular topological features compared to R8:4Br-TBS and R8:4CH-TBS complexes. These differences are attributed to the changes in the preferred orientation of the guanidino groups of R8 with respect to the π-surface of TBS derivatives. The modulation of forces of interaction across the R8:TBS-derivative coassemblies aligns with their respective thermal stabilities. The single-crystal structure of bare 4F-TBS has been subjected to Hirshfeld and 2D fingerprinting analysis and indicates notable variations from the crystal packing of the R8:4F-TBS coassembly. The structural differences among the R8:TBS-derivative coassemblies correlate with distinctive profiles of antibacterial activity in each case. The coassembled structures exert a variable extent of bacterial membrane disruption and damage based on the unique disposition of R8 and the potency of small molecule in each case. The aqueous suspension of R8:4F-TBS displays significant outer membrane disruption and bacterial killing compared with the other complexes. This work successfully demonstrates the hitherto unreported potential for coassembly of cell-penetrating peptides with other entities. The coassembly of R8 with small molecules highlights an attractive strategy for tuning the functional properties of each component.
阳离子肽八精氨酸（R8）是一种突出的细胞穿透肽，已被广泛研究作为各种细胞靶向货物的载体。在这项工作中，我们描述了 R8 与噻唑基苯磺酰胺（TBS）衍生物的共组装。R8 与三种 TBS 衍生物在一系列重量比下的物理复合导致形成一组独特的纳米和微结构。通过 FTIR、XRD、SEM 和 DSC 的组合对 R8:TBS 衍生物共组装体进行了详细的结构表征。促进共组装的主要官能团包括 TBS 衍生物的磺酰胺 SO 和 NH 基团，以及 R8 的胍基，通过阳离子-π 和氢键相互作用的组合。与 R8:4Br-TBS 和 R8:4CH-TBS 复合物相比，R8:4F-TBS 共组装显示出独特的拓扑特征。这些差异归因于 R8 的胍基相对于 TBS 衍生物的π 表面的优选取向的变化。跨 R8:TBS 衍生物共组装体的相互作用力的调制与其各自的热稳定性一致。裸露的 4F-TBS 的单晶结构已进行了 Hirshfeld 和二维指纹分析，表明与 R8:4F-TBS 共组装的晶体堆积有明显的差异。R8:TBS 衍生物共组装体之间的结构差异与每种情况下的抗菌活性的独特特征相关。共组装结构根据每种情况下 R8 的独特布置和小分子的效力对细菌膜产生不同程度的破坏和损伤。与其他复合物相比，R8:4F-TBS 的水悬浮液显示出显著的外膜破坏和细菌杀伤作用。这项工作成功地证明了细胞穿透肽与其他实体共组装的前所未有的潜力。R8 与小分子的共组装突出了一种有吸引力的策略，用于调整每个组件的功能特性。
