Synthesis and Binding Studies of G-Quadruplex Recognising Small Molecule Ligands

Gaurav, Abhiket (2011) Synthesis and Binding Studies of G-Quadruplex Recognising Small Molecule Ligands. Masters thesis, Indian Institute of Science Education and Research, Kolkata.

PDF (MS-thesis of Abhiket Gaurav) My_thesis-final.pdf Restricted to Repository staff only Download (1MB)

Abstract

Human telomeric DNA (htelo), which is located at the end of chromosomes, contains repeating single-strand sequences of(TTAGGG)n ( L. Oganesian, T. M. Bryan, BioEssays 2007, 29, 155; L. R. Kelland, Eur. J. Cancer 2005, 41, 971). This G-rich single strand forms a characteristic four-stranded helical conformation (G-quadruplex) in the presence of monovalent cations such as potassium or sodium ions. The formation of G-quadruplexes in vitro has been shown to inhibit the activity of telomerase, an enzyme related to the elongation of telomeres in tumor cells; thus, inhibiting telomerase activity by stabilizing the telomeric G-quadruplex is considered to have potential for the treatment of cancer. The G-quadruplex structure exists not only in the telomeric DNA, but also in the promoter regions of some oncogenes, such as c-myc, c-kit, and bcl-2. These DNA sequences also play significant roles in the inhibition of transcriptional activity. Therefore, sequence- and mode-selective G-quadruplex ligands would be candidate anticancer agents as well as biological tools. Most G-quadruplex ligands comprise a planar, aromatic core presumed to stack on the terminal tetrads of G-quadruplex (Monchaud, M.-P. Teulade-Fichou, Org. Biomol. Chem. 2008, 6, 627). Herein we propose the synthesis and biophysical evaluation of a new class of Gquadruplex binding ligands based on thiazole derivatives. I aim to utilize ‘click chemistry’ to prepare mono and bis-triazole containing bis-triazole amide containing ligands.

Actions (login required)

View Item