01905nas a2200181   4500008004100000022001400041245008400055210006900139260007100208300001200279490000600291520122600297100001801523700003101541700001901572700001801591856011401609       2013                        eng d  a1554-892900aMolecular-beacon-based screen for small molecule inhibitors of miRNA maturation0 aMolecularbeaconbased screen for small molecule inhibitors of miR  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcMAY  a930-9380 v83 a<p>miRNAs are small non-coding RNAs that regulate about 60% of mammalian genes by modulating their transcript levels. Network scale studies of miRNA-mediated regulatory circuits demonstrate the central importance of this class of small RNA in the maintenance of biological robustness. More recently, several reports have described the deregulation of numerous miRNA to be causally associated with many diseases, including cancer. These studies have highlighted the potential for development of therapeutic modalities against miRNA. Previous screening protocols, for small molecules targeting miRNA function, are either costly or technically too complex to be applied in a high-throughput manner in standard chemical laboratories. We describe a simple in vitro screening method using a DNA-based molecular beacon that overcomes the limitations associated with earlier screens. We used this method to identify inhibitors of miR-27a function from a library of 14 aminoglycosides as a pilot study. Inhibitory molecules identified were further scrutinized to identify the validity of screen. With this proof of concept we illustrate the utility of a scalable molecular-beacon-based screening strategy for miRNA inhibitors.</p>1 aBose, Debojit1 aJayaraj, Gopal, Gunanathan1 aKumar, Santosh1 aMaiti, Souvik  uhttps://library.ncl.res.in/content/molecular-beacon-based-screen-small-molecule-inhibitors-mirna-maturation-002196nas a2200217   4500008004100000022001400041245009200055210006900147260007100216300001400287490000700301520139700308100001801705700002701723700001901750700001601769700003101785700002301816700001801839856012101857       2014                        eng d  a0006-296000aMorphological effects of G-quadruplex stabilization using a small molecule in zebrafish0 aMorphological effects of Gquadruplex stabilization using a small  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcFEB  a1117-11240 v533 a<p>Zebrafish (Danio rerio) embryos are transparent and advantageous for studying early developmental changes due to ex utero development, making them an appropriate model for studying gene expression changes as a result of molecular targeting. Zebrafish embryos were injected with a previously reported G-quadruplex selective ligand, and the phenotypic changes were recorded. We report marked discrepancies in the development of intersegmental vessels. In silico analysis determined that the putative G-quadruplex motif occur in the upstream promoter region of the Cdh5 (N-cadherin) gene. A real-time polymerase chain reaction-based investigation indicated that in zebrafish, CDH-2 (ZN-cad) was significantly downregulated in the ligand-treated embryos. Biophysical characterization of the interaction of the ligand with the G-quadruplex motif found in this promoter yielded strong binding and stabilization of the G-quadruplex with this ligand. Hence, we report for the first time the phenotypic impact of G-quadruplex targeting with a ligand in a vertebrate organism. This study has unveiled not only G-quadruplex targeting in non-human animal species but also the potential that G-quadruplexes can provide a ready tool for understanding the phenotypic effects of targeting certain important genes involved in differentiation and developmental processes in a living eukaryotic organism.</p>1 aAgarwal, Tani1 aLalwani, Mukesh, Kumar1 aKumar, Santosh1 aRoy, Saumya1 aChakraborty, Tushar, Kanti1 aSivasubbu, Sridhar1 aMaiti, Souvik  uhttps://library.ncl.res.in/content/morphological-effects-g-quadruplex-stabilization-using-small-molecule-zebrafish-0