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The functional and therapeutic importance of the Warburg effect is increasingly recognized, and glycolysis has become a target of anticancer strategies. We recently reported the identification of a group of novel small compounds that inhibit basal glucose transport and reduce cancer cell growth by a glucose deprivation-like mechanism. We hypothesized that(More)
Ribosomal frameshifting, a translational mechanism used during retroviral replication, involves a directed change in reading frame at a specific site at a defined frequency. Such programmed frameshifting at the mouse mammary tumor virus (MMTV) gag-pro shift site requires two mRNA signals: a heptanucleotide shifty sequence and a pseudoknot structure(More)
The solution conformation of an RNA pseudoknot, which is a mutant of the pseudoknot required for ribosomal frameshifting in mouse mammary tumor virus, has been determined by NMR. The 32-nucleotide RNA pseudoknot does not promote efficient frameshifting, although its sequence is very similar to the efficient frameshifting pseudoknot whose structure was(More)
The T-box transcription antitermination regulatory system is an important mechanism for regulation of expression of aminoacyl-tRNA synthetase, amino acid biosynthesis and transporter gene expression in Gram-positive bacteria. Antitermination is dependent on a complex set of interactions between uncharged tRNA and the leader region of the mRNA of the(More)
The objective of this work was to assess the feasibility and accuracy of T1 and relaxivity measurements in cell cultures using 1.5T magnetic resonance imaging (MRI) with the long-term goal to develop a tool for evaluation of novel paramagnetic agents in a realistic macromolecular environment. This initial study was carried out using MCF-7 cells treated with(More)
The T box transcription antitermination regulatory system, found in Gram-positive bacteria, is dependent on a complex set of interactions between uncharged tRNA and the 5'-untranslated mRNA leader region of the regulated gene. One of these interactions involves the base pairing of the acceptor end of cognate tRNA with four bases in a 7 nt bulge of the(More)
Expression of many aminoacyl-tRNA synthetase, amino acid biosynthesis and transport genes in Bacillus subtilis is controlled at the level of transcription termination using the T box system and requires the formation of specific secondary structures in the mRNA leader region. One structure functions as a transcriptional terminator, while an alternate form,(More)
We have synthesized and tested a series of novel 3,4,5-tri- and 4,5-disubstituted oxazolidinones for their ability to bind two structurally related T box antiterminator model RNAs. We have found that optimal binding selectivity is found in a small group of 4,5-disubstituted oxazolidinones.
The T box transcription antitermination mechanism is found in many Gram-positive bacteria. The T box genes are typically tRNA synthetase, amino acid biosynthesis, and amino acid transport genes that have a common transcriptional control mechanism in which a unique RNA-RNA interaction occurs between an uncharged tRNA and the 5' leader region of the nascent(More)
The T box transcription antitermination system is a riboswitch found primarily in Gram-positive bacteria which monitors the aminoacylation of the cognate tRNA and regulates a variety of amino acid-related genes. Novel 4,5-disubstituted oxazolidinones were identified as high affinity RNA molecular effectors that modulate the transcription antitermination(More)