(S)-Stereoisomer of telomestatin as a potent G-quadruplex binder and telomerase inhibitor

Takayuki Doi, Kazuaki Shibata, Masahito Yoshida, Motoki Takagi, Masayuki Tera, Kazuo Nagasawa, Kazuo Shin-Ya, Takashi Takahashi

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Total synthesis of the (S)-stereoisomer of telomestatin (1) was accomplished. (S)-Telomestatin exhibited potency four times that of the natural product, (R)-telomestatin, which was the most potent telomerase inhibitor previously reported. In the circular dichroism spectral analysis of the complexes possessing randomly structured single-stranded d[TTAGGG]4 oligonucleotide, (S)-telomestatin, like (R)-telomestatin, induced an antiparallel G-quadruplex structure. The melting temperature (Tm) value of the (S)-isomer complex was greater than that of the (R)-telomestatin complex. Therefore, it is concluded that the stereochemistry of the thiazoline of telomestatin is important to the binding ability of a G-quadruplex binder, and (S)-telomestatin as a G-quadruplex binder is more potent than the natural product.

Original languageEnglish
Pages (from-to)387-393
Number of pages7
JournalOrganic and Biomolecular Chemistry
Volume9
Issue number2
DOIs
Publication statusPublished - 2011 Jan 21

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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