Department of Biochemistry, Kangwon National University, Chuncheon 24341, Republic of Korea.
Department of Biological Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
Int J Mol Sci. 2024 Sep 30;25(19):10571. doi: 10.3390/ijms251910571.
The chirality of a chemical differentiates it from its mirror-image counterpart. This unique property has significant implications in chemistry, biology, and drug discovery, where chiral chemicals display high selectivity and activity in achieving target specificity and reducing attrition rates in drug development. Stress granules (SGs) are dynamic assemblies of proteins and RNA that form in the cytoplasm of cells under stress conditions. Modulating their formation or disassembly could offer a novel approach to treating a wide range of diseases. This has led to significant interest in SGs as potential therapeutic targets. This study examined the NTF2-like domain of G3BP1 as a possible target for SG modulation. Molecular docking was used to simulate the interactions of compounds with the domain, and a potential candidate with a chiral structure was identified. The experiments showed that the compound induced the formation of SG-like granules. Importantly, the ability of this compound to modulate SG offers valuable insights into a new mechanism underlying the dynamics and promoting the assembly of SGs, and this new mechanism, in turn, holds potential for the development of drugs with diverse mechanisms of action and potentially synergistic effects.
手性是化学物质与其镜像物质区分开来的特性。这种独特的性质在手性化学、生物学和药物发现中具有重要意义，因为手性化学物质在实现靶向特异性和降低药物开发中的损耗率方面表现出高度的选择性和活性。应激颗粒（SGs）是蛋白质和 RNA 在细胞细胞质中形成的动态组装体，在应激条件下。调节它们的形成或解体可能为治疗广泛的疾病提供一种新的方法。这导致了对 SG 作为潜在治疗靶点的极大兴趣。本研究检查了 G3BP1 的 NTF2 样结构域作为 SG 调节的可能靶点。分子对接用于模拟化合物与该结构域的相互作用，并确定了一个具有手性结构的潜在候选物。实验表明，该化合物诱导 SG 样颗粒的形成。重要的是，该化合物调节 SG 的能力为 SG 动力学和促进 SG 组装的新机制提供了有价值的见解，而这种新机制反过来又为具有多种作用机制和潜在协同作用的药物的开发提供了潜力。
