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


Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
22 05 2023
Historique:
accepted: 12 03 2023
revised: 03 02 2023
received: 13 10 2022
medline: 23 5 2023
pubmed: 28 3 2023
entrez: 27 3 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 36971129
pii: 7086672
doi: 10.1093/nar/gkad189
pmc: PMC10201448
doi:

Substances chimiques

Alkylating Agents 0
DNA 9007-49-2
Ligands 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4112-4125

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.

Références

Front Chem. 2018 Jul 24;6:281
pubmed: 30137743
Biochemistry. 2005 Feb 15;44(6):2048-58
pubmed: 15697230
Bioorg Med Chem. 2014 Aug 15;22(16):4407-18
pubmed: 24957878
ChemMedChem. 2019 May 6;14(9):889-906
pubmed: 30816012
Nucleic Acids Res. 2021 Jul 9;49(12):6638-6659
pubmed: 33978760
Nat Chem. 2018 Jun;10(6):631-637
pubmed: 29686376
Biochem Biophys Res Commun. 2000 Nov 11;278(1):158-66
pubmed: 11071868
Photodiagnosis Photodyn Ther. 2005 Sep;2(3):175-91
pubmed: 25048768
Biochemistry. 2016 Apr 19;55(15):2291-9
pubmed: 27027664
J Am Chem Soc. 2014 Apr 23;136(16):5860-3
pubmed: 24697838
Pharmaceuticals (Basel). 2020 Dec 25;14(1):
pubmed: 33375595
Analyst. 2011 Jul 7;136(13):2692-6
pubmed: 21566850
Nature. 2015 May 14;521(7551):232-6
pubmed: 25915022
Front Chem. 2020 Jan 23;8:4
pubmed: 32039162
J Am Chem Soc. 2004 Jul 21;126(28):8702-9
pubmed: 15250722
J Am Chem Soc. 2012 Jul 4;134(26):10737-40
pubmed: 22698383
Chem Sci. 2020 Oct 9;11(43):11729-11739
pubmed: 34094412
Nucleic Acids Res. 2019 Jul 26;47(13):6578-6589
pubmed: 31188442
Chemistry. 2015 Feb 2;21(6):2330-4
pubmed: 25512076
Nat Methods. 2005 Apr;2(4):261-7
pubmed: 15782218
Chem Commun (Camb). 2021 Jan 25;57(8):1010-1013
pubmed: 33404017
J Am Chem Soc. 2020 Dec 9;142(49):20600-20604
pubmed: 33253551
Angew Chem Int Ed Engl. 2008;47(26):4858-61
pubmed: 18496803
Bioorg Med Chem. 2018 Jul 23;26(12):3551-3558
pubmed: 29807700
Nat Rev Drug Discov. 2022 Dec;21(12):881-898
pubmed: 36008483
Science. 2015 Jul 17;349(6245):
pubmed: 26089354
Nucleic Acid Ther. 2019 Feb;29(1):1-12
pubmed: 30307373
Nat Rev Genet. 2012 Nov;13(11):770-80
pubmed: 23032257
J Am Chem Soc. 2009 Sep 16;131(36):13132-41
pubmed: 19694465
Nucleic Acids Res. 2005 Jul 28;33(13):4182-90
pubmed: 16052031
RSC Chem Biol. 2022 Jul 21;3(9):1129-1143
pubmed: 36128507
Chem Sci. 2017 Nov 1;8(11):7448-7456
pubmed: 29163897
Nat Rev Drug Discov. 2011 Apr;10(4):307-17
pubmed: 21455239
Nucleic Acids Res. 2020 May 21;48(9):4627-4642
pubmed: 32282912
Nucleic Acids Res. 2007;35(10):3367-74
pubmed: 17478520
J Am Chem Soc. 2009 Sep 23;131(37):13399-409
pubmed: 19705869
Nucleic Acids Res. 2017 Apr 7;45(6):2951-2959
pubmed: 28180276
Angew Chem Int Ed Engl. 2014 Jan 20;53(4):994-8
pubmed: 24338872
Nature. 1993 Jun 10;363(6429):561-5
pubmed: 8389423
J Am Chem Soc. 2014 Feb 5;136(5):1750-3
pubmed: 24450880
Chem Commun (Camb). 2018 Feb 15;54(15):1897-1900
pubmed: 29393312
Nucleic Acids Res. 2018 Sep 19;46(16):8038-8056
pubmed: 30124962
Cell. 2015 Apr 9;161(2):404-16
pubmed: 25843628
Nat Commun. 2015 Apr 27;6:6952
pubmed: 25914116
J Am Chem Soc. 2017 Jun 28;139(25):8522-8536
pubmed: 28570076
Chemistry. 2019 Jan 7;25(2):417-430
pubmed: 30051593
Chem Res Toxicol. 2009 Jan;22(1):24-34
pubmed: 19149477
Biochemistry. 1998 Sep 1;37(35):12331-42
pubmed: 9724547
Org Biomol Chem. 2017 Jul 21;15(27):5669-5673
pubmed: 28567459
Nat Commun. 2016 Oct 26;7:13304
pubmed: 27782131
Nucleic Acids Res. 2020 Dec 2;48(21):11942-11957
pubmed: 33137181
Nat Rev Drug Discov. 2020 Oct;19(10):673-694
pubmed: 32782413
Molecules. 2019 Feb 06;24(3):
pubmed: 30736276
Clin Transl Oncol. 2008 Mar;10(3):148-54
pubmed: 18321817
Pharmaceuticals (Basel). 2021 Jul 13;14(7):
pubmed: 34358095
Biopolymers. 2021 Dec;112(12):e23460
pubmed: 34129732
Sci Adv. 2022 Oct 7;8(40):eabo0522
pubmed: 36197984
Mol Biosyst. 2017 Jul 25;13(8):1458-1468
pubmed: 28650023
Chemistry. 2022 Jun 21;28(35):e202200734
pubmed: 35441438
Nucleic Acids Res. 2022 Jul 22;50(13):7247-7259
pubmed: 35801856
Nature. 1953 Apr 25;171(4356):737-8
pubmed: 13054692
Genes (Basel). 2020 Nov 12;11(11):
pubmed: 33198362
Chem Pharm Bull (Tokyo). 2018;66(12):1091-1103
pubmed: 30504626
J Biol Chem. 2019 Apr 12;294(15):5890-5895
pubmed: 30787104
Nat Commun. 2019 Sep 16;10(1):4205
pubmed: 31527589
Nucleic Acids Res. 2006 May 10;34(9):2536-49
pubmed: 16687659

Auteurs

Enrico Cadoni (E)

Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium.

Lessandro De Paepe (L)

Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium.

Gertjan Colpaert (G)

Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium.

Ruben Tack (R)

Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium.

Dries Waegeman (D)

Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium.

Alex Manicardi (A)

Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium.

Annemieke Madder (A)

Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium.

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Classifications MeSH