4.6 Article

Pyridyl-Substituted Corrole Isomers: Synthesis and their Regulation to G-quadruplex Structures

Journal

CHEMISTRY-AN ASIAN JOURNAL
Volume 5, Issue 1, Pages 114-122

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/asia.200900270

Keywords

G-quadruplex; sequences selectivity; corroles; structure induction; telomerase inhibitor

Funding

  1. National Science of Foundation of China [20672084, 90813031, 20621502]
  2. National Key Foundation for Infectious Diseases [2008ZX10003-005]
  3. State Key Laboratory of Bio-Organic & Natural Products Chemistry Shanghai Institute of Organic Chemistry
  4. Chinese Academy of Sciences Shanghai (P.R. China) [200032]
  5. State Key Laboratory of Natural and Biomimetic Drugs
  6. Peking University

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G-quadruplex DNA plays an important role in the potential therapeutic target for the design and development of anticancer drugs. As various G-quadruplex sequences in the promoter regions or telomeres can form different secondary structural modes and display a diversity of biology functions, variant G-quadruplex interactive agents may be necessary to cure different disease by differentiating variant types of G-quadruplexes. We synthesize five cationic methylpyridylium corroles and compare the interactions of corroles with different types of G-quadruplexes such as cmyc, htelo, and bcl2 by using surface plasmon resonance. Because of the importance of human telomere G-quadruplex DNA, we focus on the biological properties of the interactions between human telomere G-quadruplex DNA and corrole isomers using CD, T-m, PCR-stop (PCR = polymerase chain reaction), and polymerase-stop assay, which demonstrate the excellent ability of the corrole to induce and stabilize the G-quadruplex. This study provides the first experimental insight into how selectivity might be achieved for different G-quadruplexes by a single group of methylpyridylium corrole isomers that may be optimized for potential selective cancer therapy.

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