DNA loop sequence as the determinant for chiral supramolecular compound G-quadruplex selectivity.
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, beta-galactosidase activity, and up-regulation of cyclin-dependent kinase inhibitors p16 and p21.
Yu
Haijia
H
Division of Biological Inorganic Chemistry, State Key Laboratory of Rare Earth Resource Utilization, Graduate School of the Chinese Academy of Sciences, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
Zhao
Chuanqi
C
Chen
Yong
Y
Fu
Manliang
M
Ren
Jinsong
J
Qu
Xiaogang
X
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000737:chemistry / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D019098:Telomerase / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D046911:Macromolecular Substances; D004247:DNA; D019098:Telomerase