Chemically modified aptamers for improving binding affinity to the target proteins via enhanced non-covalent bonding

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Yihao Zhang¹  Amu Gubu²  Hong Dai³  Hang Luo³  Zefeng Chen³  Ge Zhang⁴  Yuan Ma⁴  Aiping Lu⁴  Baoting Zhang⁵  Sifan Yu⁵  Huarui Zhang⁵ 

[1] Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China;Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China;Aptacure Therapeutics Limited, Kowloon, Hong Kong SAR, China;Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China;Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China;Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China;Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China;Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, Hong Kong SAR, China;School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China;

关键词: aptamer;    chemical modification;    high affinity;    non-covalent bonding;    interaction;   

DOI  :  10.3389/fcell.2023.1091809

 received in 2022-11-07, accepted in 2023-02-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

Nucleic acid aptamers are ssDNA or ssRNA fragments that specifically recognize targets. However, the pharmacodynamic properties of natural aptamers consisting of 4 naturally occurring nucleosides (A, G, C, T/U) are generally restricted for inferior binding affinity than the cognate antibodies. The development of high-affinity modification strategies has attracted extensive attention in aptamer applications. Chemically modified aptamers with stable three-dimensional shapes can tightly interact with the target proteins via enhanced non-covalent bonding, possibly resulting in hundreds of affinity enhancements. This review overviewed high-affinity modification strategies used in aptamers, including nucleobase modifications, fluorine modifications (2′-fluoro nucleic acid, 2′-fluoro arabino nucleic acid, 2′,2′-difluoro nucleic acid), structural alteration modifications (locked nucleic acid, unlocked nucleic acid), phosphate modifications (phosphorothioates, phosphorodithioates), and extended alphabets. The review emphasized how these high-affinity modifications function in effect as the interactions with target proteins, thereby refining the pharmacodynamic properties of aptamers.

【 授权许可】

Unknown   
Copyright © 2023 Chen, Luo, Gubu, Yu, Zhang, Dai, Zhang, Zhang, Ma, Lu and Zhang.