PloS one, 2013-01, Vol.8 (1), p.e53962-e53962
2013
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Aminoglycosylation can enhance the G-quadruplex binding activity of epigallocatechin
- Ist Teil von
- PloS one, 2013-01, Vol.8 (1), p.e53962-e53962
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- With the aim of enhancing G-quadruplex binding activity, two new glucosaminosides (16, 18) of penta-methylated epigallocatechin were synthesized by chemical glycosylation. Subsequent ESI-TOF-MS analysis demonstrated that these two glucosaminoside derivatives exhibit much stronger binding activity to human telomeric DNA and RNA G-quadruplexes than their parent structure (i.e., methylated EGC) (14) as well as natural epigallocatechin (EGC, 6). The DNA G-quadruplex binding activity of 16 and 18 is even more potent than strong G-quadruplex binder quercetin, which has a more planar structure. These two synthetic compounds also showed a higher binding strength to human telomeric RNA G-quadruplex than its DNA counterpart. Analysis of the structure-activity relationship revealed that the more basic compound, 16, has a higher binding capacity with DNA and RNA G-quadruplexes than its N-acetyl derivative, 18, suggesting the importance of the basicity of the aminoglycoside for G-quadruplex binding activity. Molecular docking simulation predicted that the aromatic ring of 16 π-stacks with the aromatic ring of guanine nucleotides, with the glucosamine moiety residing in the groove of G-quadruplex. This research indicates that glycosylation of natural products with aminosugar can significantly enhance their G-quadruplex binding activities, thus is an effective way to generate small molecules targeting G-quadruplexes in nucleic acids. In addition, this is the first report that green tea catechin can bind to nucleic acid G-quadruplex structures.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0053962Titel-ID: cdi_plos_journals_1289058592
- Format
- –
- Schlagworte
- Analysis, Basicity, Binding, Biology, Cancer, Catechin, Catechin - analogs & derivatives, Catechin - chemistry, Catechin - metabolism, Chemical synthesis, Chemistry, Deoxyribonucleic acid, Design, DNA, DNA - chemistry, DNA - metabolism, G-Quadruplexes, Glucosamine, Glycosylation, Green tea, Guanine, Humans, Laboratories, Ligands, Mass spectrometry, Medicine, Models, Molecular, Molecular docking, Natural products, Nucleic acids, Nucleotides, Oncogenes, Physics, Purines, Quercetin, Ribonucleic acid, RNA, RNA - genetics, RNA - metabolism, Scientific imaging, Simulation, Tea, Telomerase, Telomere - chemistry