title: Aminoglycosylation can enhance the G-quadruplex binding activity of epigallocatechin.
abstract: 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.
authors: State Key Laboratory of Quality Research in Chinese Medicine, and Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau.
authors: Li-Ping
authors: LP
authors: Bai
authors: Hing-Man
authors: HM
authors: Ho
authors: Dik-Lung
authors: DL
authors: Ma
authors: Hui
authors: H
authors: Yang
authors: Wai-Chung
authors: WC
authors: Fu
authors: Zhi-Hong
authors: ZH
authors: Jiang
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D054856:G-Quadruplexes; D006031:Glycosylation; D006801:Humans; D008958:Models, Molecular; D009857:Oncogenes; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000737:chemistry
chemical_list: D012313:RNA; D002392:Catechin; D004247:DNA; C057580:gallocatechol