Generation of Biostable L-aptamers against Achiral Targets by Chiral Inversion of Existing D-aptamers

Huapei Chen; Sitao Xie; Hao Liang; Cuichen Wu; Liang Cui; Shuang-Yan Huan; Xiaobing Zhang

doi:10.1016/j.talanta.2016.11.001

Generation of Biostable L-aptamers against Achiral Targets by Chiral Inversion of Existing D-aptamers

Talanta. 2017 Mar 1:164:662-667. doi: 10.1016/j.talanta.2016.11.001. Epub 2016 Nov 3.

Authors

Huapei Chen¹, Sitao Xie¹, Hao Liang¹, Cuichen Wu², Liang Cui³, Shuang-Yan Huan¹, Xiaobing Zhang⁴

Affiliations

¹ Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082, China.
² Attribute Sciences, Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320, United States.
³ Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082, China. Electronic address: [email protected].
⁴ Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University, Changsha 410082, China. Electronic address: [email protected].

PMID: 28107987
DOI: 10.1016/j.talanta.2016.11.001

Abstract

In this paper, based on reciprocal chiral substrate specificity, taking achiral molecules, ethanolamine (EA) and malachite green (MG) as two model targets, biostable L- DNA aptamers and L-RNA aptamers were generated respectively by chiral inversion of existing D-aptamers. In the detection of EA with L-DNA aptamer-based sensors, the feasibility of our strategy was confirmed, while in the detection of MG with L-RNA aptamers, linear calibration curves were obtained in the range from 0.1 to 5µm with the detection limit of 0.065µm under optimized experimental conditions. The results demonstrated that the mirror-image L-aptamers have identical recognition capability as D-aptamers. Meanwhile, L-aptamers have superior biostability to resist nuclease digestion, protein binding interference and off-target effects, enabling their applications in complex practical samples, such as lake water and fish tissue extractions. Our work provides a simple, yet universal and efficient way to develop biostable aptamers.

Keywords: Aptamers; Biostability; Ethanolamine; Malachite green; Mirror image.

MeSH terms

Aptamers, Nucleotide / chemistry*
Drug Stability
Ethanolamine / chemistry
Rosaniline Dyes / chemistry
Stereoisomerism
Substrate Specificity

Substances

Aptamers, Nucleotide
Rosaniline Dyes
malachite green
Ethanolamine