Targeting Guanine Quadruplexes with Luminescent Platinum(II) Complexes Bearing a Pendant Nucleobase.

Chempluschem

Westfälische Wilhelms-Universität Münster, Institut für Anorganische und Analytische Chemie, Corrensstr. 30, 48149, Münster, Germany.

Published: April 2021

AI Article Synopsis

  • Guanine quadruplexes are interesting tetra-stranded nucleic acid structures that could lead to new anticancer treatments due to their unique properties.
  • The complex nature of guanine quadruplexes makes it hard to specifically target certain sequences, which is a challenge for therapeutic development.
  • Researchers are creating luminescent platinum(II) complexes with extra nucleobases attached to improve targeting capabilities and have begun to evaluate how different nucleobase attachments affect the metal complex's affinity for various DNA sequences.

Article Abstract

Guanine quadruplexes are tetra-stranded nucleic acid structures currently raising significant interest in the context of the development of potential anticancer therapeutics with a new mode of action. They are composed of planar guanine tetrads, allowing a high-affinity targeting by using molecules with a large π surface. However, the extreme topological versatility of guanine quadruplexes impedes a straightforward targeting of particular preselected guanine-rich sequences. We report here a systematic study of a family of luminescent platinum(II) complexes devised to overcome this challenge. By attaching a pendant adenine or thymine nucleobase as a substituent to one of the ligands at the platinum center, an additional recognition site is introduced with the aim of modulating the affinity of the metal complex to different DNA sequences. By comparing different attached nucleobases and a series of linker moieties, first conclusions are drawn with respect to the scope of this approach.

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Source
http://dx.doi.org/10.1002/cplu.202100135DOI Listing

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