Dangerous, antibiotic resistant bacteria have been observed with increasing frequency over the past several decades. In this review the factors that have been linked to this phenomenon are addressed. Profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated. Factors including economic impact, intrinsic… (More)
This Nano Focus article highlights recent advances in RNA nanotechnology as presented at the First International Conference of RNA Nanotechnology and Therapeutics, which took place in Cleveland, OH, USA (October 23-25, 2010) ( http://www.eng.uc.edu/nanomedicine/RNA2010/ ), chaired by Peixuan Guo and co-chaired by David Rueda and Scott Tenenbaum. The… (More)
The molecular structure of the DNA double helix has been known for 60 years, but we remain surprisingly ignorant of the balance of forces that determine its mechanical properties. The DNA double helix is among the stiffest of all biopolymers, but neither theory nor experiment has provided a coherent understanding of the relative roles of attractive base… (More)
A highly emissive nucleobase analog, based on a thieno[3,4-d]pyrimidine core, is enzymatically incorporated into RNA oilgonucleotides that function as base discriminating fluorescent probes.
The lack of high RNA target selectivity displayed by aminoglycoside antibiotics results from both their electrostatically driven binding mode and their conformational adaptability. The inherent flexibility around their glycosidic bonds allows them to easily assume a variety of conformations, permitting them to structurally adapt to diverse RNA targets. This… (More)
A family of extended 5-modified-6-aza-uridines was obtained via Suzuki coupling reactions with a common brominated precursor. Extending the conjugated-6-aza-uridines with substituted aryl rings increases the push-pull interactions yielding enhanced bathochromic shifts and solvatochromism compared to the parent nucleosides. For example, the methoxy… (More)
A number of aminoglycoside antibiotics, and in particular neomycin B, are demonstrated to promote strand cleavage of RNA oligonucleotides (minimised HIV-1 TAR element and prokaryotic ribosomal A-site), by binding and causing sufficient distortion to the RNA backbone to render it more susceptible to intramolecular transesterification.
A FRET assembly reports antibiotic affinities to two different RNA targets. A binder was labeled with a fluorophore that acts both as an acceptor for the emissive nucleoside on the bacterial A-site and a donor fluorophore for the terminally-labeled human A-site. Unlabeled drugs were used to dissociate the labeled antibiotic.
Semisynthetic derivatives of the clinically useful aminoglycosides tobramycin and amikacin were prepared by selectively modifying their 6'' positions with a variety of hydrogen bond donors and acceptors. Their binding to the rRNA A-site was probed using an in vitro FRET-based assay, and their antibacterial activities against several resistant strains (e.g.,… (More)