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

Zefeng Chen, Hang Luo, Amu Gubu, Sifan Yu, Huarui Zhang, Hong Dai, Yihao Zhang, Baoting Zhang, Yuan Ma*, Aiping Lu*, Ge Zhang*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

10 Citations (Scopus)

Abstract

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.
Original languageEnglish
Article number1091809
Number of pages12
JournalFrontiers in Cell and Developmental Biology
Volume11
DOIs
Publication statusPublished - 23 Feb 2023

User-Defined Keywords

  • aptamer
  • chemical modification
  • high affinity
  • interaction
  • non-covalent bonding

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