TY - JOUR
T1 - Chemically modified aptamers for improving binding affinity to the target proteins via enhanced non-covalent bonding
AU - Chen, Zefeng
AU - Luo, Hang
AU - Gubu, Amu
AU - Yu, Sifan
AU - Zhang, Huarui
AU - Dai, Hong
AU - Zhang, Yihao
AU - Zhang, Baoting
AU - Ma, Yuan
AU - Lu, Aiping
AU - Zhang, Ge
N1 - Funding Information:
This study was supported by the Guangdong Basic and Applied Basic Research Foundation (2020A1515110630), the Hong Kong General Research Fund (HKBU 12114416, HKBU 12101117, HKBU 12100918, HKBU 12101018, HKBU 12103519, and HKBU 14100218), the National Key R&D Program of China (2018YFA0800804).
Publisher Copyright:
Copyright © 2023 Chen, Luo, Gubu, Yu, Zhang, Dai, Zhang, Zhang, Ma, Lu and Zhang.
PY - 2023/2/23
Y1 - 2023/2/23
N2 - 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.
AB - 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.
KW - aptamer
KW - chemical modification
KW - high affinity
KW - interaction
KW - non-covalent bonding
UR - http://www.scopus.com/inward/record.url?scp=85149894110&partnerID=8YFLogxK
U2 - 10.3389/fcell.2023.1091809
DO - 10.3389/fcell.2023.1091809
M3 - Journal article
C2 - 36910146
SN - 2296-634X
VL - 11
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 1091809
ER -
