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A red light-triggered chemical tool for sequence-specific alkylation of G-quadruplex and I-motif DNA

Enrico Cadoni (UGent) , Lessandro De Paepe (UGent) , Gertjan Colpaert (UGent) , Ruben Tack (UGent) , Dries Waegeman, Alex Manicardi (UGent) and Annemieke Madder (UGent)
(2023) NUCLEIC ACIDS RESEARCH. 51(9). p.4112-4125
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Abstract
The importance of non-canonical DNA structures such as G-quadruplexes (G4) and intercalating-motifs (iMs) in the fine regulation of a variety of cellular processes has been recently demonstrated. As the crucial roles of these structures are being unravelled, it is becoming more and more important to develop tools that allow targeting these structures with the highest possible specificity. While targeting methodologies have been reported for G4s, this is not the case for iMs, as evidenced by the limited number of specific ligands able to bind the latter and the total absence of selective alkylating agents for their covalent targeting. Furthermore, strategies for the sequence-specific covalent targeting of G4s and iMs have not been reported thus far. Herein, we describe a simple methodology to achieve sequence-specific covalent targeting of G4 and iM DNA structures based on the combination of (i) a peptide nucleic acid (PNA) recognizing a specific sequence of interest, (ii) a pro-reactive moiety enabling a controlled alkylation reaction, and (iii) a G4 or iM ligand orienting the alkylating warhead to the reactive residues. This multi-component system allows for the targeting of specific G4 or iM sequences of interest in the presence of competing DNA sequences and under biologically relevant conditions.
Keywords
C-MYC PROMOTER, PHOTODYNAMIC THERAPY, BINDING, STABILITY, LIGAND, IDENTIFICATION, ELEMENT, OLIGONUCLEOTIDES, ADOPTS

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MLA
Cadoni, Enrico, et al. “A Red Light-Triggered Chemical Tool for Sequence-Specific Alkylation of G-Quadruplex and I-Motif DNA.” NUCLEIC ACIDS RESEARCH, vol. 51, no. 9, 2023, pp. 4112–25, doi:10.1093/nar/gkad189.
APA
Cadoni, E., De Paepe, L., Colpaert, G., Tack, R., Waegeman, D., Manicardi, A., & Madder, A. (2023). A red light-triggered chemical tool for sequence-specific alkylation of G-quadruplex and I-motif DNA. NUCLEIC ACIDS RESEARCH, 51(9), 4112–4125. https://doi.org/10.1093/nar/gkad189
Chicago author-date
Cadoni, Enrico, Lessandro De Paepe, Gertjan Colpaert, Ruben Tack, Dries Waegeman, Alex Manicardi, and Annemieke Madder. 2023. “A Red Light-Triggered Chemical Tool for Sequence-Specific Alkylation of G-Quadruplex and I-Motif DNA.” NUCLEIC ACIDS RESEARCH 51 (9): 4112–25. https://doi.org/10.1093/nar/gkad189.
Chicago author-date (all authors)
Cadoni, Enrico, Lessandro De Paepe, Gertjan Colpaert, Ruben Tack, Dries Waegeman, Alex Manicardi, and Annemieke Madder. 2023. “A Red Light-Triggered Chemical Tool for Sequence-Specific Alkylation of G-Quadruplex and I-Motif DNA.” NUCLEIC ACIDS RESEARCH 51 (9): 4112–4125. doi:10.1093/nar/gkad189.
Vancouver
1.
Cadoni E, De Paepe L, Colpaert G, Tack R, Waegeman D, Manicardi A, et al. A red light-triggered chemical tool for sequence-specific alkylation of G-quadruplex and I-motif DNA. NUCLEIC ACIDS RESEARCH. 2023;51(9):4112–25.
IEEE
[1]
E. Cadoni et al., “A red light-triggered chemical tool for sequence-specific alkylation of G-quadruplex and I-motif DNA,” NUCLEIC ACIDS RESEARCH, vol. 51, no. 9, pp. 4112–4125, 2023.
@article{01GZ9DHNMP3Z24NC9YK58QNARV,
  abstract     = {{The importance of non-canonical DNA structures such as G-quadruplexes (G4) and intercalating-motifs (iMs) in the fine regulation of a variety of cellular processes has been recently demonstrated. As the crucial roles of these structures are being unravelled, it is becoming more and more important to develop tools that allow targeting these structures with the highest possible specificity. While targeting methodologies have been reported for G4s, this is not the case for iMs, as evidenced by the limited number of specific ligands able to bind the latter and the total absence of selective alkylating agents for their covalent targeting. Furthermore, strategies for the sequence-specific covalent targeting of G4s and iMs have not been reported thus far. Herein, we describe a simple methodology to achieve sequence-specific covalent targeting of G4 and iM DNA structures based on the combination of (i) a peptide nucleic acid (PNA) recognizing a specific sequence of interest, (ii) a pro-reactive moiety enabling a controlled alkylation reaction, and (iii) a G4 or iM ligand orienting the alkylating warhead to the reactive residues. This multi-component system allows for the targeting of specific G4 or iM sequences of interest in the presence of competing DNA sequences and under biologically relevant conditions.}},
  author       = {{Cadoni, Enrico and De Paepe, Lessandro and Colpaert, Gertjan and Tack, Ruben and Waegeman, Dries and Manicardi, Alex and Madder, Annemieke}},
  issn         = {{0305-1048}},
  journal      = {{NUCLEIC ACIDS RESEARCH}},
  keywords     = {{C-MYC PROMOTER,PHOTODYNAMIC THERAPY,BINDING,STABILITY,LIGAND,IDENTIFICATION,ELEMENT,OLIGONUCLEOTIDES,ADOPTS}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{4112--4125}},
  title        = {{A red light-triggered chemical tool for sequence-specific alkylation of G-quadruplex and I-motif DNA}},
  url          = {{http://doi.org/10.1093/nar/gkad189}},
  volume       = {{51}},
  year         = {{2023}},
}

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