01803nas a2200193   4500008004100000022001400041245007300055210006900128260011000197300001400307490000600321520109200327100001701419700001801436700001501454700001801469700001801487856010401505       2015                        eng d  a2041-652000aPotent inhibition of miR-27a by neomycin-bisbenzimidazole conjugates0 aPotent inhibition of miR27a by neomycinbisbenzimidazole conjugat  aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcJUL  a5837-58460 v63 a<p>miRNAs are important components of regulatory networks that control gene expression and have implications in various diseases including cancer. Targeting oncogenic miRNAs with small molecules is currently being explored to develop cancer therapeutics. Here, we report the development of dual binding neomycin-bisbenzimidazole conjugates that target oncogenic miR-27a with high affinity (K-a = 1.2 to 7.4 x 10(8) M-1). These conjugates bring significant reduction (similar to 65% at 5 mu M) in mature miRNA levels and penetrate easily in the cells where they localise both in the cytoplasm and the nucleus. Cell cycle analysis showed significant increase in the G0/G1 phase (similar to 15%) and decrease in the S phase (similar to 7%) upon treatment with neomycin-bisbenzimidazole conjugates, suggesting inhibition of cell proliferation. Using the conjugation approach, we show that moderately binding ligands can be covalently combined into high affinity binders. This study also highlights the role of linker optimization in designing high affinity ligands for miR-27a targeting.</p>1 aNahar, Smita1 aRanjan, Nihar1 aRay, Arjun1 aArya, Dev, P.1 aMaiti, Souvik  uhttps://library.ncl.res.in/content/potent-inhibition-mir-27a-neomycin-bisbenzimidazole-conjugates-0