DNA Loop Sequence as the Determinant for Chiral Supramolecular Compound G-Quadruplex Selectivity
journal contributionposted on 14.01.2010, 00:00 by Haijia Yu, Chuanqi Zhao, Yong Chen, Manliang Fu, Jinsong Ren, Xiaogang Qu
It is important to develop G-quadruplex binding agents that can discriminate between different quadruplexes. Recently we reported the first example that a chiral supramolecular complex can selectively stabilize human telomeric G-quadruplex among different G-quadruplex and duplex DNA, and the two enantiomers show different inhibition effect on telomerase activity. Here, we report that DNA loop sequence can be determinant for this chiral complex G-quadruplex selectivity. Adenine in the diagonal loop plays an important role in G-quadruplex hybrid structural transition, thus, it strongly influences the chiral complex induced DNA structural transition. The complex’s preference for human telomeric DNA and its chiral selectivity prompted us to investigate whether the two enantiomers, M and P, can show different effects on cancer cells. The P enantiomer’s chiral selectivity has been demonstrated in cancer cells by telomere shortening, β-galactosidase activity, and up-regulation of cyclin-dependent kinase inhibitors p16 and p21.