Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/79475
Title: Selective lighting up of epiberberine alkaloid fluorescence by fluorophore-switching aptamer and stoichiometric targeting of human telomeric DNA G-quadruplex multimer
Authors: Zhang, Lihua
Liu, Hua
Shao, Yong
Lin, Clement
Jia, Huan
Chen, Gang
Yang, Danzhou
Wang, Ying
Keywords: DRNTU::Science::Chemistry::Biochemistry
Issue Date: 2014
Source: Zhang, L., Liu, H., Shao, Y., Lin, C., Jia, H., Chen, G., et al. (2014). Selective lighting up of epiberberine alkaloid fluorescence by fluorophore-switching aptamer and stoichiometric targeting of human telomeric DNA G-quadruplex multimer. Analytical chemistry, 87(1), 730-737.
Series/Report no.: Analytical chemistry
Abstract: Aptamers, that exist naturally in living cells as functional elements and can switch nonfluorescent natural targets to fluorophores, are very useful in developing highly sensitive and selective biosensors and screening functional agents. This work demonstrates that human telomeric G-quadruplex (HTG) can serve as a potential fluorophore-switching aptamer (FSA) to target a natural isoquinoline alkaloid. We found that, among the G-quadruplexes studied here and the various structurally similar alkaloids including epiberberine (EPI), berberine (BER), palmatine (PAL), jatrorrhizine (JAT), coptisine (COP), worenine (WOR), sanguinarine (SAN), chelerythrine (CHE), and nitidine (NIT), only the HTG DNA, especially with a 5′-TA-3′ residue at the 5′ end of the G-quadruplex tetrad (5′-TAG3(TTAG3)3-3′, TA[Q]) as the minimal sequence, is the most efficient FSA to selectively light up the EPI fluorescence. Compared to the 5′ end flanking sequences, the 3′ end flanking sequences of the tetrad contribute significantly less to the recognition of EPI. The binding affinity of EPI to TA[Q] (Kd = 37 nM) is at least 20 times tighter than those of the other alkaloids. The steady-state absorption, steady-state/time-resolved fluorescence, and NMR studies demonstrate that EPI most likely interact with the 5′ end flanking sequence substructure beyond the core [Q] and the G-quadruplex tetrad in a much more specific manner than the other alkaloids. The highly selective and tight binding of EPI with the FSA and significantly enhanced fluorescence suggest the potential development of a selective EPI sensor (detection limit of 10 nM). More importantly, EPI, as the brightest FSA emitter among the alkaloids, can also serve as an efficient conformation probe for HTG DNA and discriminate the DNA G-quadruplex from the RNA counterpart. Furthermore, EPI can bind stoichiometrically to each G-quadruplex unit of long HTG DNA multimer with the most significant fluorescence enhancement, which has not been achieved by the previously reported probes. Our work suggests the potential use of EPI as a bioimaging probe and a therapeutic DNA binder.
URI: https://hdl.handle.net/10356/79475
http://hdl.handle.net/10220/25093
ISSN: 0003-2700
DOI: 10.1021/ac503730j
Rights: © 2014 American Chemical Society. This is the author created version of a work that has been peer reviewed and accepted for publication by Analytical Chemistry, American Chemical Society. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1021/ac503730j].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SPMS Journal Articles

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