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从头蛋白质设计能为血液系统疾病的治疗带来什么?

What Can De Novo Protein Design Bring to the Treatment of Hematological Disorders?

作者信息

Lu Hui, Cheng Zhipeng, Hu Yu, Tang Liang V

机构信息

Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

出版信息

Biology (Basel). 2023 Jan 20;12(2):166. doi: 10.3390/biology12020166.

Abstract

Protein therapeutics have been widely used to treat hematological disorders. With the advent of de novo protein design, protein therapeutics are not limited to ameliorating natural proteins but also produce novel protein sequences, folds, and functions with shapes and functions customized to bind to the therapeutic targets. De novo protein techniques have been widely used biomedically to design novel diagnostic and therapeutic drugs, novel vaccines, and novel biological materials. In addition, de novo protein design has provided new options for treating hematological disorders. Scientists have designed protein switches called Colocalization-dependent Latching Orthogonal Cage-Key pRoteins (Co-LOCKR) that perform computations on the surface of cells. De novo designed molecules exhibit a better capacity than the currently available tyrosine kinase inhibitors in chronic myeloid leukemia therapy. De novo designed protein neoleukin-2/15 enhances chimeric antigen receptor T-cell activity. This new technique has great biomedical potential, especially in exploring new treatment methods for hematological disorders. This review discusses the development of de novo protein design and its biological applications, with emphasis on the treatment of hematological disorders.

摘要

蛋白质疗法已被广泛用于治疗血液系统疾病。随着从头蛋白质设计的出现,蛋白质疗法不仅限于改善天然蛋白质,还能产生具有定制形状和功能的新型蛋白质序列、折叠结构和功能,以结合治疗靶点。从头蛋白质技术已在生物医学领域广泛应用于设计新型诊断和治疗药物、新型疫苗以及新型生物材料。此外,从头蛋白质设计为治疗血液系统疾病提供了新的选择。科学家们设计了一种名为共定位依赖性锁定正交笼钥蛋白(Co-LOCKR)的蛋白质开关,它能在细胞表面进行计算。从头设计的分子在慢性髓性白血病治疗中表现出比现有酪氨酸激酶抑制剂更好的疗效。从头设计的蛋白质新白细胞介素-2/15增强了嵌合抗原受体T细胞的活性。这项新技术具有巨大的生物医学潜力,尤其是在探索血液系统疾病的新治疗方法方面。本文综述了从头蛋白质设计的发展及其生物学应用,重点讨论了其在血液系统疾病治疗中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd86/9952452/359d0cba35cb/biology-12-00166-g001.jpg

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