Analytical Chemistry
Analytical Chemistry
5 years ago

Prototropically Allosteric Probe for Superbly Selective DNA Analysis

Prototropically Allosteric Probe for Superbly Selective DNA Analysis
Zhiai Xu, Hui Wang, Benoit Habermeyer, Xinghua Shi, Yufeng Zhou, Qiusha Li, Yong Shao, Fan Lin, Xiaoshun Zhou
Selective nucleotide recognition for biosensor evolution requires rational probe design toward the binding-pattern-susceptible readout but without serious poison in selectivity from the context sequences. In this work, we synthesized a dual-function (trihydroxyphenyl)porphyrin (POH3) to target the abasic site (AP site) in ds-DNA using the trihydroxyphenyl substituent and the tetrapyrrole macrocycle as the recognition unit (RU) and the fluorescent signal unit (SU), respectively. RU and SU are separated from each other but are prototropically allosteric. We found that an appropriate pH favors formation of the nonfluorescent quinine/pyrrole (O–NH) conformer of POH3. However, the complementary hydrogen bonding of RU in O–NH with the target cytosine opposite the AP site switches on the SU fluorescence through prototropic allostery toward the phenol/isopyrrole (OH–N) conformer, while the bases thymine, guanine, and adenine totally silence this allostery, suggesting a superb selectivity in single-nucleotide polymorphism (SNP) analysis. The role of the prototropic allostery in achieving such SNP selectivity is also evidenced using porphyrins with other hydroxyl substituent patterns. Because of the SU separation from RU, SU is not directly involved in the interaction with the AP site, and thus, the turn-on selectivity is also realized for DNA with flanking guanine, the most easily oxidized base in DNA. This tolerance to the flanking base identity has seldom been achieved in previous studies. Additionally, other DNA structures cannot bring this allostery, indicating that the combination recipe of the AP site design and the prototropically allosteric probe will find wide applications in DNA-based sensors.

Publisher URL: http://dx.doi.org/10.1021/acs.analchem.7b02077

DOI: 10.1021/acs.analchem.7b02077

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.