Umeå University's logo

umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A complementary chemical probe approach towards customized studies of G-quadruplex DNA structures in live cells
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Science and Technology, Department of Chemistry.ORCID iD: 0000-0001-8089-2333
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Show others and affiliations
2022 (English)In: Chemical Science, ISSN 2041-6520, E-ISSN 2041-6539, Vol. 13, no 8, p. 2347-2354Article in journal (Refereed) Published
Abstract [en]

G-quadruplex (G4) DNA structures are implicated in central biological processes and are considered promising therapeutic targets because of their links to human diseases such as cancer. However, functional details of how, when, and why G4 DNA structures form in vivo are largely missing leaving a knowledge gap that requires tailored chemical biology studies in relevant live-cell model systems. Towards this end, we developed a synthetic platform to generate complementary chemical probes centered around one of the most effective and selective G4 stabilizing compounds, Phen-DC3. We used a structure-based design and substantial synthetic devlopments to equip Phen-DC3 with an amine in a position that does not interfere with G4 interactions. We next used this reactive handle to conjugate a BODIPY fluorophore to Phen-DC3. This generated a fluorescent derivative with retained G4 selectivity, G4 stabilization, and cellular effect that revealed the localization and function of Phen-DC3 in human cells. To increase cellular uptake, a second chemical probe with a conjugated cell-penetrating peptide was prepared using the same amine-substituted Phen-DC3 derivative. The cell-penetrating peptide conjugation, while retaining G4 selectivity and stabilization, increased nuclear localization and cellular effects, showcasing the potential of this method to modulate and direct cellular uptake e.g. as delivery vehicles. The applied approach to generate multiple tailored biochemical tools based on the same core structure can thus be used to advance the studies of G4 biology to uncover molecular details and therapeutic approaches. This journal is

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2022. Vol. 13, no 8, p. 2347-2354
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-193064DOI: 10.1039/d1sc05816aISI: 000751956900001Scopus ID: 2-s2.0-85125772577OAI: oai:DiVA.org:umu-193064DiVA, id: diva2:1646239
Funder
Swedish Research Council, VR-NT 2017-05235The Kempe Foundations, SMK-1632Knut and Alice Wallenberg Foundation, VR-MH 2018-0278EU, Horizon 2020, 751474Available from: 2022-03-21 Created: 2022-03-21 Last updated: 2023-03-24Bibliographically approved

Open Access in DiVA

fulltext(847 kB)151 downloads
File information
File name FULLTEXT01.pdfFile size 847 kBChecksum SHA-512
8397999b52cdc461361878bd5bffb493fa060c3e4ae5f1e56abf523b3cc0fedc4ca2828b531233bdb350b73bba3d577ac78bbcc8997b7f3f7e24dea3159e4f26
Type fulltextMimetype application/pdf

Other links

Publisher's full textScopus

Authority records

Prasad, BagineniDoimo, MaraAndréasson, MånsL'Hôte, ValentinChorell, ErikWanrooij, Sjoerd

Search in DiVA

By author/editor
Prasad, BagineniDoimo, MaraAndréasson, MånsL'Hôte, ValentinChorell, ErikWanrooij, Sjoerd
By organisation
Department of ChemistryDepartment of Medical Biochemistry and Biophysics
In the same journal
Chemical Science
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 151 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 789 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf