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 d...

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Main Authors: Zefeng Chen, Hang Luo, Amu Gubu, Sifan Yu, Huarui Zhang, Hong Dai, Yihao Zhang, Baoting Zhang, Yuan Ma, Aiping Lu, Ge Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2023.1091809/full
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author Zefeng Chen
Zefeng Chen
Hang Luo
Hang Luo
Amu Gubu
Amu Gubu
Sifan Yu
Huarui Zhang
Hong Dai
Hong Dai
Yihao Zhang
Baoting Zhang
Yuan Ma
Yuan Ma
Yuan Ma
Aiping Lu
Aiping Lu
Aiping Lu
Ge Zhang
Ge Zhang
Ge Zhang
author_facet Zefeng Chen
Zefeng Chen
Hang Luo
Hang Luo
Amu Gubu
Amu Gubu
Sifan Yu
Huarui Zhang
Hong Dai
Hong Dai
Yihao Zhang
Baoting Zhang
Yuan Ma
Yuan Ma
Yuan Ma
Aiping Lu
Aiping Lu
Aiping Lu
Ge Zhang
Ge Zhang
Ge Zhang
author_sort Zefeng Chen
collection DOAJ
description 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.
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spelling doaj.art-f336ff8690354fe8abbf208b6b1c734a2023-02-23T12:43:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-02-011110.3389/fcell.2023.10918091091809Chemically modified aptamers for improving binding affinity to the target proteins via enhanced non-covalent bondingZefeng Chen0Zefeng Chen1Hang Luo2Hang Luo3Amu Gubu4Amu Gubu5Sifan Yu6Huarui Zhang7Hong Dai8Hong Dai9Yihao Zhang10Baoting Zhang11Yuan Ma12Yuan Ma13Yuan Ma14Aiping Lu15Aiping Lu16Aiping Lu17Ge Zhang18Ge Zhang19Ge Zhang20Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaAptacure Therapeutics Limited, Kowloon, Hong Kong SAR, ChinaSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, Hong Kong SAR, ChinaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, Hong Kong SAR, ChinaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, ChinaInstitute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, Hong Kong SAR, ChinaNucleic 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.https://www.frontiersin.org/articles/10.3389/fcell.2023.1091809/fullaptamerchemical modificationhigh affinitynon-covalent bondinginteraction
spellingShingle Zefeng Chen
Zefeng Chen
Hang Luo
Hang Luo
Amu Gubu
Amu Gubu
Sifan Yu
Huarui Zhang
Hong Dai
Hong Dai
Yihao Zhang
Baoting Zhang
Yuan Ma
Yuan Ma
Yuan Ma
Aiping Lu
Aiping Lu
Aiping Lu
Ge Zhang
Ge Zhang
Ge Zhang
Chemically modified aptamers for improving binding affinity to the target proteins via enhanced non-covalent bonding
Frontiers in Cell and Developmental Biology
aptamer
chemical modification
high affinity
non-covalent bonding
interaction
title Chemically modified aptamers for improving binding affinity to the target proteins via enhanced non-covalent bonding
title_full Chemically modified aptamers for improving binding affinity to the target proteins via enhanced non-covalent bonding
title_fullStr Chemically modified aptamers for improving binding affinity to the target proteins via enhanced non-covalent bonding
title_full_unstemmed Chemically modified aptamers for improving binding affinity to the target proteins via enhanced non-covalent bonding
title_short Chemically modified aptamers for improving binding affinity to the target proteins via enhanced non-covalent bonding
title_sort chemically modified aptamers for improving binding affinity to the target proteins via enhanced non covalent bonding
topic aptamer
chemical modification
high affinity
non-covalent bonding
interaction
url https://www.frontiersin.org/articles/10.3389/fcell.2023.1091809/full
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