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G4-ligand-conjugate...
G4-ligand-conjugated oligonucleotides mediate selective binding and stabilization of individual G4 DNA structures
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- Berner, Andreas (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Das, Rabindra Nath (author)
- Umeå universitet,Kemiska institutionen
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- Bhuma, Naresh (author)
- Umeå universitet,Kemiska institutionen
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- Golebiewska, Justyna (author)
- Umeå universitet,Kemiska institutionen
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- Abrahamsson, Alva (author)
- Umeå universitet,Kemiska institutionen
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- Andréasson, Måns, 1994- (author)
- Umeå universitet,Kemiska institutionen
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- Chaudhari, Namrata (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Doimo, Mara (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Bose, Partha Pratim (author)
- Department of Biosciences and Nutrition, Karolinska Institutet, Neo, Huddinge, Sweden
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- Chand, Karam (author)
- Umeå universitet,Kemiska institutionen
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- Strömberg, Roger (author)
- Karolinska Institutet
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- Wanrooij, Sjoerd (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Chorell, Erik (author)
- Umeå universitet,Kemiska institutionen
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(creator_code:org_t)
- American Chemical Society (ACS), 2023
- 2023
- English.
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 146:10, s. 6926-6935
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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Abstract
Subject headings
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- G-quadruplex (G4) DNA structures are prevalent secondary DNA structures implicated in fundamental cellular functions, such as replication and transcription. Furthermore, G4 structures are directly correlated to human diseases such as cancer and have been highlighted as promising therapeutic targets for their ability to regulate disease-causing genes, e.g., oncogenes. Small molecules that bind and stabilize these structures are thus valuable from a therapeutic perspective and helpful in studying the biological functions of the G4 structures. However, there are hundreds of thousands of G4 DNA motifs in the human genome, and a long-standing problem in the field is how to achieve specificity among these different G4 structures. Here, we developed a strategy to selectively target an individual G4 DNA structure. The strategy is based on a ligand that binds and stabilizes G4s without selectivity, conjugated to a guide oligonucleotide, that specifically directs the G4-Ligand-conjugated oligo (GL-O) to the single target G4 structure. By employing various biophysical and biochemical techniques, we show that the developed method enables the targeting of a unique, specific G4 structure without impacting other off-target G4 formations. Considering the vast amount of G4s in the human genome, this represents a promising strategy to study the presence and functions of individual G4s but may also hold potential as a future therapeutic modality.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Berner, Andreas
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Das, Rabindra Na ...
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Bhuma, Naresh
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Golebiewska, Jus ...
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Abrahamsson, Alv ...
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Andréasson, Måns ...
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Chaudhari, Namra ...
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Doimo, Mara
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Bose, Partha Pra ...
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Chand, Karam
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Strömberg, Roger
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Wanrooij, Sjoerd
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Chorell, Erik
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
- Articles in the publication
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Journal of the A ...
- By the university
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Umeå University
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Karolinska Institutet