14-3-3σ在控制肿瘤代谢重编程和癌细胞生长中起着重要作用。然而，在许多癌症中，由于下调，其功能常常受到损害。先前的研究发现，14-3-3σ的同型二聚体化对其活性至关重要。然而，至今尚不清楚稳定14-3-3σ同型二聚体是否可以提高其活性或防止其降解。在我们之前的工作中，我们曾显示GCP-Lys-OMe是一个潜在的14-3-3σ同型二聚体稳定剂。然而，其稳定作用尚未经过实验验证。因此，在本研究中，我们尝试使用与之前描述的GCP-Lys-OMe类似的体外技术来预测几个可能稳定14-3-3σ二聚体形式的肽段。随后的[1H]-CPMG NMR实验证实了这些肽段（肽段3、5、9和16）与14-3-3σ的结合，其中肽段3显示最强的结合。竞争性[1H]-CPMG测定进一步表明，肽段3与14-3-3σ结合肽（ExoS）不竞争其在蛋白的两亲沟槽上的结合，但有助于提高14-3-3σ对ExoS蛋白的结合。当14-3-3σ经历动态光散射实验时，发现其同型二聚体在聚集之前会解离成单体。有趣的是，肽段3的存在增加了14-3-3σ对聚集的稳定性。总体而言，我们的发现表明：（1）结合分子对接和分子动力学模拟可以用于发现潜在的14-3-3σ同型二聚体稳定化合物；（2）肽段3可以减缓14-3-3σ的聚集（可能是通过防止其解离成单体），并且提高14-3-3σ与ExoS蛋白的结合能力。

14-3-3σ plays an important role in controlling tumor metabolic reprogramming and cancer cell growth. However, its function is often compromised in many cancers due to its downregulation. Previous studies found that homodimerization of 14-3-3σ is critical for its activity. However, to date, it is not known if stabilization of 14-3-3σ homodimers can improve its activity or prevent its degradation. In our previous work, we have showed that GCP-Lys-OMe is a potential 14-3-3σ homodimer stabilizer. However, its stabilizing effect was not experimentally validated. Therefore, in this study, we have attempted to predict few potential peptides that can stabilize the dimeric form of 14-3-3σ using similar in silico techniques as described previously for GCP-Lys-OMe. Subsequent [1H]-CPMG NMR experiments confirmed the binding of the peptides (peptides 3, 5, 9, and 16) on 14-3-3σ, with peptide 3 showing the strongest binding. Competitive [1H]-CPMG assays further revealed that while peptide 3 does not compete with a 14-3-3σ binding peptide (ExoS) for the protein's amphipathic groove, it was found to improve ExoS binding on 14-3-3σ. When 14-3-3σ was subjected to dynamic light scattering experiments, the 14-3-3σ homodimer was found to undergo dissociation into monomers prior to aggregation. Intriguingly, the presence of peptide 3 increased 14-3-3σ stability against aggregation. Overall, our findings suggest that (1) docking accompanied by MD simulations can be used to identify potential homodimer stabilizing compounds of 14-3-3σ and (2) peptide 3 can slow down 14-3-3σ aggregation (presumably by preventing its dissociation into monomers), as well as improving the binding of 14-3-3σ to ExoS protein.