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
Exploring the dispersion and electrostatic components in arene-arene interactions between ligands and G4 DNA to develop G4-ligands
Umeå University, Faculty of Science and Technology, Department of Chemistry.ORCID iD: 0000-0001-8089-2333
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.ORCID iD: 0009-0004-3292-1637
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Show others and affiliations
2024 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 67, no 3, p. 2202-2219Article in journal (Refereed) Published
Abstract [en]

G-Quadruplex (G4) DNA structures are important regulatory elements in central biological processes. Small molecules that selectively bind and stabilize G4 structures have therapeutic potential, and there are currently >1000 known G4 ligands. Despite this, only two G4 ligands ever made it to clinical trials. In this work, we synthesized several heterocyclic G4 ligands and studied their interactions with G4s (e.g., G4s from the c-MYC, c-KIT, and BCL-2 promoters) using biochemical assays. We further studied the effect of selected compounds on cell viability, the effect on the number of G4s in cells, and their pharmacokinetic properties. This identified potent G4 ligands with suitable properties and further revealed that the dispersion component in arene-arene interactions in combination with electron-deficient electrostatics is central for the ligand to bind with the G4 efficiently. The presented design strategy can be applied in the further development of G4-ligands with suitable properties to explore G4s as therapeutic targets.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2024. Vol. 67, no 3, p. 2202-2219
National Category
Medicinal Chemistry
Identifiers
URN: urn:nbn:se:umu:diva-220319DOI: 10.1021/acs.jmedchem.3c02127PubMedID: 38241609Scopus ID: 2-s2.0-85183093324OAI: oai:DiVA.org:umu-220319DiVA, id: diva2:1837204
Funder
The Kempe Foundations, JCK-3159The Kempe Foundations, SMK-1632Swedish Research Council, 2017-05235Swedish Research Council, 2021-04805Knut and Alice Wallenberg FoundationAvailable from: 2024-02-13 Created: 2024-02-13 Last updated: 2024-07-02Bibliographically approved

Open Access in DiVA

fulltext(5866 kB)83 downloads
File information
File name FULLTEXT01.pdfFile size 5866 kBChecksum SHA-512
1030a2440a352eff202667a466e30c55142bba302ff4ffa0750ac0b2d12769a71b631999aa10af2ec68d021b516c850d8920c34a2b7298cc4f4970af0e51af9a
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records

Andréasson, MånsDonzel, MaximeAbrahamsson, AlvaBerner, AndreasDoimo, MaraQuiroga, AnnaEriksson, Anna U.Wanrooij, SjoerdChorell, Erik

Search in DiVA

By author/editor
Andréasson, MånsDonzel, MaximeAbrahamsson, AlvaBerner, AndreasDoimo, MaraQuiroga, AnnaEriksson, Anna U.Wanrooij, SjoerdChorell, Erik
By organisation
Department of ChemistryDepartment of Medical Biochemistry and Biophysics
In the same journal
Journal of Medicinal Chemistry
Medicinal Chemistry

Search outside of DiVA

GoogleGoogle Scholar
Total: 83 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
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 304 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