Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design.

中文翻译：

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抗体片段在结构上能够促进针对癌症靶点 Mcl-1 的药物发现活动。


细胞凋亡是多细胞生物控制组织生长、去除和炎症的关键过程。在癌症中经常观察到正常凋亡功能的破坏，通过过度表达 Bcl-2（B 细胞淋巴瘤 2）家族（包括 Mcl-1（骨髓细胞白血病 1））抗凋亡蛋白来避免细胞死亡。这使得Mcl-1成为药物治疗的潜在靶点，通过抑制Mcl-1的保护功能，可以恢复正常的细胞凋亡。在此，描述了抗 Mcl-1 抗体片段的发现和生物物理特性，并证明了 scFv 和 Fab 在生成适合迭代结构指导药物设计的 Mcl-1 晶体系统中的效用。