Sefid Fateme, Payandeh Zahra, Azamirad Ghasem, Baradaran Behzad, Nabi Afjadi Mohsen, Islami Maryam, Darvish Maryam, Kalantar Seyed Mehdi, Kahroba Houman, Ardakani Mahnam Alaei
Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran.
Department of Biology, Science and Art University, Yazd, Iran.
In Silico Pharmacol. 2021 Feb 15;9(1):20. doi: 10.1007/s40203-021-00076-z. eCollection 2021.
CD274 gene encodes programmed death-ligand 1 (PD-L1) protein, also known as B7 homolog 1 (B7-H1), which is a crucial hallmark for highly proliferation cells including cancer cells. PD-1 and PD-L1 interaction is assumed as a negative regulator for immune response which can inhibit the T cell growth and cytokine secretion and supports tumor cells evasion from immune system. therefore, PD-L1 could be assumed as a candidate target for immune-therapy. The predicted structure of PD-L1 indicates (Gly4Ser) 3 linker-based chains links. In that line, different simulation softwares applied to explore the structure of granzyme B (GrB), a serine protease in cytotoxic lymphocytes granules as an apoptosis mediator, was attached to its specific antibody structure (atezolizumab) via an adaptor sequence. Evaluation of accuracy, energy minimization and characterization of biological properties of the final processed structure were performed and our computational outcomes indicated that the employed method for structure prediction has been successfully managed to design the immunotoxin structure. It is necessary to mention that, the precise and accurate design of the immune-therapeutic agents against cancer cells can be confirmed by employment of in-silico approaches. Consequently, based on this approach we could introduce a capable immunotoxin which specifically targeting PD-L1 in an accurate orientation and initiates cancer cell destruction by its toxin domain.
The online version contains supplementary material available at 10.1007/s40203-021-00076-z.
CD274基因编码程序性死亡配体1（PD-L1）蛋白，也称为B7同源物1（B7-H1），它是包括癌细胞在内的高度增殖细胞的关键标志。PD-1与PD-L1的相互作用被认为是免疫反应的负调节因子，可抑制T细胞生长和细胞因子分泌，并支持肿瘤细胞逃避免疫系统。因此，PD-L1可被视为免疫治疗的候选靶点。PD-L1的预测结构表明基于（Gly4Ser）3接头的链连接。在这方面，应用不同的模拟软件来探索颗粒酶B（GrB）的结构，颗粒酶B是细胞毒性淋巴细胞颗粒中的一种丝氨酸蛋白酶，作为一种凋亡介质，通过接头序列与它的特异性抗体结构（阿特珠单抗）相连。对最终处理结构的准确性、能量最小化和生物学特性进行了评估，我们的计算结果表明，所采用的结构预测方法已成功设计出免疫毒素结构。需要指出的是，通过计算机模拟方法可以证实针对癌细胞的免疫治疗药物的精确设计。因此，基于这种方法，我们可以引入一种有能力的免疫毒素，它以精确的方向特异性靶向PD-L1，并通过其毒素结构域引发癌细胞的破坏。
在线版本包含可在10.1007/s40203-021-00076-z获取的补充材料。
