Qureshi Shahnila, Ahmed Nadeem, Rehman Hafiz Muhammad, Amirzada Muhammad Imran, Saleem Fiza, Waheed Kainat, Chaudhry Afeefa, Kafait Iram, Akram Muhammad, Bashir Hamid
Centre for Applied Molecular Biology, University of the Punjab, 87-West canal, Bank Road, Lahore, 53700 Pakistan.
Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, 87-West canal, Bank Road, Lahore, 53700 Pakistan.
In Silico Pharmacol. 2024 Sep 18;12(2):84. doi: 10.1007/s40203-024-00252-x. eCollection 2024.
Targeted delivery of therapeutic anticancer chimeric molecules enhances drug efficacy. Numerous studies have focused on developing novel treatments by employing cytokines, particularly interleukins, to inhibit the growth of cancer cells. In the present study, we fused interleukin 24 with the tumor-targeting peptide P20 through a rigid linker to selectively target cancer cells. The secondary structure, tertiary structure, and physicochemical characteristics of the constructed chimeric IL-24-P20 protein were predicted by using bioinformatics tools. In-silico analysis revealed that the fusion construct has a basic nature with 175 amino acids and a molecular weight of 20 kDa. By using the Rampage and ERRAT2 servers, the validity and quality of the fusion protein were evaluated. The results indicated that 93% of the chimeric proteins contained 90.1% of the residues in the favoured region, resulting in a reliable structure. Finally, docking and simulation studies were conducted via ClusPro and Desmond Schrödinger, respectively. Our results indicate that the constructed fusion protein exhibits excellent quality, interaction capabilities, validity, and stability. These findings suggest that the fusion protein is a promising candidate for targeted cancer therapy.
治疗性抗癌嵌合分子的靶向递送可提高药物疗效。众多研究聚焦于通过利用细胞因子,尤其是白细胞介素,来开发抑制癌细胞生长的新疗法。在本研究中,我们通过刚性连接子将白细胞介素24与肿瘤靶向肽P20融合,以选择性地靶向癌细胞。利用生物信息学工具预测了构建的嵌合IL-24-P20蛋白的二级结构、三级结构和理化特性。计算机模拟分析表明,该融合构建体呈碱性,含有175个氨基酸,分子量为20 kDa。通过使用Rampage和ERRAT2服务器,评估了融合蛋白的有效性和质量。结果表明,93%的嵌合蛋白在有利区域含有90.1%的残基,从而形成了可靠的结构。最后,分别通过ClusPro和Desmond Schrödinger进行对接和模拟研究。我们的结果表明,构建的融合蛋白具有优异的质量、相互作用能力、有效性和稳定性。这些发现表明,该融合蛋白是靶向癌症治疗的一个有前景的候选物。