第36卷，第3期 2016年3月
光谱学与光谱分析 Spectroscopy and Spectral Analysis
Vol. 36,No. 3,pp896-902
March,2016
SpectralAnalysisofInteractionbetweenHumanTelomeric
G-Quadruplex andLiliflorinA,theFirstLignan DerivativeInteractedwithG-QuadruplexDNA
LIU Ting-ting", ZHOU Shuang', JIA Qian-lan', WANG Wen-shul-2* YAN Xiao-qian', ZHANG Wen-hao",WANG Shuai-qi', JIAO Yu-guo
1, College of Life and Environmental Sciences, Minzu University of Chins, Beijing100081, China
2. Bejing Engineering Research Center of Food Environment and Health, Minzu University of Chins, Beijing100081, China 3. Center of Biomedical Analysis, Tsinghua University, Beijing100084, Chins
Human telomeric G-quadruplex is a four-stranded structure folded by guanines (G) via Hoogsteen
Abstract
hydrogen bonding. The ligands which stabilize the G-quadruplex are often telomerase inhibitors and may be come antitumor agents, Here, the interaction between a lignan derivative liliflorin A and human telomeric se-quence dGGG(TTAGGG);G-quadruplex HTG21 were examined by CD, FRET, and NMR spectroscopic methods. In addition, Molecular Docking was used to study the binding of liliflorin A to dTAGGG(TTAGGG);G-quadruplex HTG23. The CD data showed that liliflorin A enhanced HTG21 T.. The T, value of G-quadruplex was enhanced 3. 2 'C by 4. 0 μmol · L1 liliflorin A in FRET. The NMR spectra of HTG21 showed vivid alteration after reacting with liflorin A in 3 hours, Molecular Docking suggested liliflorin A bound to the wide groove of HTG23 at G9, G10, G16 and G17. Liliflorin A was the first lignan derivative that could stabilize HTG21 selectively and provided a new candidate for antitumor drug design targeting on hurnan telomerie G-quadruplex.
KeywordsLiliflorin A; G-quadruplex; Human telomere; Spectral analysis; Interaction
DOI: 10. 3964/j issn, 10000593(2016)030896-07
中图分类号：0657.3 Introduction
文献标识码：A
cant bioprocesses', Telomerase is a cancer-specific reverse transcriptase activated in 80% ~90% of tumors, and ex
In the process of screening bioactive compounds, spectral analysis could give straightforward, vivid and sensitive infor mation for chemical reactions between ligand and biomacro-molecule which makes the screening fast and efficiently. Gua-nine-rich DNA sequences in tivo, such as telomeric DNA se quence Tel21,Tel26 and oncogenepromoter regions (c-myc bcl-2, or c-kit), can form G-quadruplex via Hoogsteen hydro gen bonding, which plays an important role in many signifi-
pressed in very low levels or almost undetectable in normal cells(), It is reported that when telomeric DNA sequence formed G-quadruplex, it becomes insensitive to the elongation by the telomerase, which is a significant biological process for cells to proliferate, Thus, ligands binding to and stabilizing telomeric G-quadruplex could inhibit the activity of telomerase and induce apoptosis of tumors.
However, the low selectivity of the reported ligands over duplex DNA and other DNA folded structures lead to their
Received; 2015-05-08; accepted; 2015-11-02
Foundation item: The National Natural Science Foundation of China (31200260), The First-class University and the First-rate Discipline Con
struction Projects of Minzu University of China (YLDX01013, 2015MDTD08C), together with 111 Project (B08044), The National College Students' innovation and entrepreneurship training program (GCCX 2014110017, GCCX 2015110012)
Biography: LIU Ting-ting, (1987-), Doctoral Candidate of College Life and Environmental Sciences, Minzu University of China
e-mail;liutingting1204163,com
Corresponding author
万方数据
e-mail;wangws@muc edu cn