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

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.

Automated summary

Nucleic acid aptamers are single-stranded DNA or RNA fragments that can specifically recognize targets. However, natural aptamers composed of 4 naturally occurring nucleosides often have inferior binding affinity compared to antibodies. To address this, various high-affinity modification strategies have been developed, such as nucleobase modifications, fluorine modifications, structural alteration modifications, phosphate modifications, and extended alphabets. These modifications enhance the non-covalent bonding between the modified aptamers and target proteins, resulting in significantly improved affinity. This review provides an overview of these high-affinity modification strategies and their effects on the pharmacodynamic properties of aptamers.