Supramolecular Recognition of Cytidine Phosphate in Nucleotides and RNA Sequences

Morozov B, Oshchepkov AS, Klemt I, Agafontsev A, Krishna S, Hampel F, Xu H, Mokhir A, Guldi DM, Kataev E (2022)

Publication Type: Journal article

Publication year: 2022

Journal

JACS Au American Chemical Society

DOI: 10.1021/jacsau.2c00658

Abstract

Supramolecular recognition of nucleotides would enable manipulating crucial biochemical pathways like transcription and translation directly and with high precision. Therefore, it offers great promise in medicinal applications, not least in treating cancer or viral infections. This work presents a universal supramolecular approach to target nucleoside phosphates in nucleotides and RNA. The artificial active site in new receptors simultaneously realizes several binding and sensing mechanisms: encapsulation of a nucleobase via dispersion and hydrogen bonding interactions, recognition of the phosphate residue, and a self-reporting feature─“turn-on” fluorescence. Key to the high selectivity is the conscious separation of phosphate- and nucleobase-binding sites by introducing specific spacers in the receptor structure. We have tuned the spacers to achieve high binding affinity and selectivity for cytidine 5′ triphosphate coupled to a record 60-fold fluorescence enhancement. The resulting structures are also the first functional models of poly(rC)-binding protein coordinating specifically to C-rich RNA oligomers, e.g., the 5′-AUCCC(C/U) sequence present in poliovirus type 1 and the human transcriptome. The receptors bind to RNA in human ovarian cells A2780, causing strong cytotoxicity at 800 nM. The performance, self-reporting property, and tunability of our approach open up a promising and unique avenue for sequence-specific RNA binding in cells by using low-molecular-weight artificial receptors.

Authors with CRIS profile

Boris Morozov Lehrstuhl für Organische Chemie II Insa Klemt Professur für Organische Chemie Aleksandr Agafontsev Lehrstuhl für Organische Chemie II Swathi Krishna Lehrstuhl für Physikalische Chemie I Frank Hampel Lehrstuhl für Organische Chemie I Honggui Xu Professur für Organische Chemie Andriy Mokhir Professur für Organische Chemie Dirk Michael Guldi Lehrstuhl für Physikalische Chemie I Evgeny Kataev Lehrstuhl für Organische Chemie I

Involved external institutions

Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE)

How to cite

APA:

Morozov, B., Oshchepkov, A.S., Klemt, I., Agafontsev, A., Krishna, S., Hampel, F.,... Kataev, E. (2022). Supramolecular Recognition of Cytidine Phosphate in Nucleotides and RNA Sequences. JACS Au. https://doi.org/10.1021/jacsau.2c00658

MLA:

Morozov, Boris, et al. "Supramolecular Recognition of Cytidine Phosphate in Nucleotides and RNA Sequences." JACS Au (2022).

BibTeX: Download