Search: onr:"swepub:oai:gup.ub.gu.se/328428" >
A Click Chemistry-B...
A Click Chemistry-Based Artificial Metallo-Nuclease
-
- Gibney, A. (author)
- Dublin City University
-
- de Paiva, R. E. F. (author)
- Dublin City University
-
- Singh, Vandana, 1985 (author)
- Massachusetts Institute of Technology (MIT),Chalmers tekniska högskola,Chalmers University of Technology
-
show more...
-
Fox, R. (author)
-
- Thompson, D. (author)
- University Of Limerick
-
- Hennessy, J. (author)
- Dublin City University
-
- Slator, C. (author)
- Dublin City University
-
- McKenzie, C. J. (author)
- Syddansk Universitet,University of Southern Denmark
-
- Johansson, Pegah, 1978 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine,Sahlgrenska universitetssjukhuset,Sahlgrenska University Hospital,University of Gothenburg
-
- McKee, V. (author)
- Dublin City University,Syddansk Universitet,University of Southern Denmark
-
- Westerlund, Fredrik, 1978 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
-
- Kellett, A. (author)
- Dublin City University
-
show less...
-
(creator_code:org_t)
- 2023
- 2023
- English.
-
In: Angewandte Chemie-International Edition. - 1433-7851 .- 1521-3773. ; 62:38
- Related links:
-
https://research.cha... (primary) (free)
-
show more...
-
https://gup.ub.gu.se...
-
https://doi.org/10.1...
-
https://research.cha...
-
show less...
Abstract
Subject headings
Close
- Artificial metallo-nucleases (AMNs) are promising DNA damaging drug candidates. Here, we demonstrate how the 1,2,3-triazole linker produced by the Cu-catalysed azide-alkyne cycloaddition (CuAAC) reaction can be directed to build Cu-binding AMN scaffolds. We selected biologically inert reaction partners tris(azidomethyl)mesitylene and ethynyl-thiophene to develop TC-Thio, a bioactive C-3-symmetric ligand in which three thiophene-triazole moieties are positioned around a central mesitylene core. The ligand was characterised by X-ray crystallography and forms multinuclear Cu-II and Cu-I complexes identified by mass spectrometry and rationalised by density functional theory (DFT). Upon Cu coordination, Cu-II-TC-Thio becomes a potent DNA binding and cleaving agent. Mechanistic studies reveal DNA recognition occurs exclusively at the minor groove with subsequent oxidative damage promoted through a superoxide- and peroxide-dependent pathway. Single molecule imaging of DNA isolated from peripheral blood mononuclear cells shows that the complex has comparable activity to the clinical drug temozolomide, causing DNA damage that is recognised by a combination of base excision repair (BER) enzymes.
Subject headings
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Click Chemistry
- Copper
- DNA Damage
- Nuclease
- Nuclease
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Gibney, A.
-
de Paiva, R. E. ...
-
Singh, Vandana, ...
-
Fox, R.
-
Thompson, D.
-
Hennessy, J.
-
show more...
-
Slator, C.
-
McKenzie, C. J.
-
Johansson, Pegah ...
-
McKee, V.
-
Westerlund, Fred ...
-
Kellett, A.
-
show less...
- About the subject
-
- NATURAL SCIENCES
-
NATURAL SCIENCES
-
and Chemical Science ...
-
- NATURAL SCIENCES
-
NATURAL SCIENCES
-
and Biological Scien ...
-
and Biochemistry and ...
- Articles in the publication
-
Angewandte Chemi ...
- By the university
-
University of Gothenburg
-
Chalmers University of Technology