Abstract: The invention is directed to 3-?-D-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and pharmaceutical compositions containing such compounds that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds.

Abstract: The present invention relates to recombinant hepatitis C virus (HCV)-derived nucleic acids and to stable cell clones derived from human hepatoma Huh-7 cell line supporting high titer replication of said recombinant HCV nucleic acids. The subgenomic HCV replicons and cell clones of the instant invention represent the in vitro system of choice for studies of HCV propagation, anti-viral drug screening, and vaccine development.

Abstract: The present method relates to the translational activation of genes using the ribosome recruitment protein, eIF4G or an eIF4G-like protein. The invention relates to the translation of RNA molecules containing heterologous protein-binding sites, which RNA molecules encode one, two, three or more proteins. The invention provides products and methods for the identification of RNA-binding proteins. The invention further provides a system by which protein—protein interactions and inhibitors or enhancers of these interactions may be identified. Further, the invention provides products and methods to provide a cell with one or more therapeutic proteins. The invention provides products and methods for controlling the levels of translation of such proteins. The invention provides products and methods to control the translation and stoichiometry of multiple subunit proteins.

Abstract: The present invention provides methods for screening for bioactive compounds, in particular those that bind to RNA sequences involved in the pathogenesis of disease or in regulation of a physiological function. The methods involve assessing the stability and/or the conformation of an RNA target in the presence and absence of test ligands, and identifying as a ligand any test ligand that causes a measurable change in target RNA stability and/or conformation. In a preferred embodiment, the effect of a ligand on target RNA stability and/or conformation is assessed by measuring the fluorescence polarization of a fluorescently labeled probe.

Abstract: The invention provides novel yeast cells comprising genes whose expression can be modulated by growth in the presence or absence of metal ions, methods for making such yeast cells, and methods of using such yeast cells for determining the requirement for expression of particular genes for the growth or viability of the yeast cells. The invention also provides methods of using such yeast cells in the isolation, screening and analysis of candidate antifungal compounds.

Abstract: The invention provides screening methods for detecting and identifying compounds that bind to fungal specific target proteins and nucleic acids, as well as compounds which, upon binding or otherwise interacting with the target protein, can inhibit fungal growth, a method of preventing or inhibiting fungal growth in culture, a method of preventing or inhibiting fungal growth in a mammal and a method of studying pathogenic mycetes using such nucleic acid and/or protein sequences. Particularly preferred is the inhibition of the fungus Candida albicans.

Abstract: The present invention provides methods for high-throughput screening for bioactive compounds, in particular those that bind to RNA sequences involved in the pathogenesis of disease or in regulation of a physiological function. The methods involve measuring the conformation of an RNA target in the presence and absence of test ligands, and identifying as a ligand any test ligand that causes a measurable change in target RNA conformation.

Abstract: The present invention relates to recombinant hepatitis C virus (HCV)-derived nucleic acids and to stable rapidly growing cell clones derived from human hepatoma Huh-7 cell line and supporting high titer replication of said recombinant HCV nucleic acids. The subgenomic HCV replicons and cell clones of the instant invention represent the in vitro system of choice for studies of HCV propagation, anti-viral drug screening, and vaccine development.

Abstract: The present invention relates to a recombinant organism, and a bacterial strain such as Staphylococcus, and S. aureus, in particular. The organism has a regulatable gene for encoding an RNA polymerase specificity factor required for expression of at least one gene essential for growth of the organism. The regulatable gene is one which is responsive to an exogenous effector molecule, and may in particular be an inducer-responsive gene including an operator site, such as a lac operator, to which a repressor, such as a lacl-encoded repressor, is capable of binding. The regulatable gene may in particular be an IPTG responsive plaC allele.

Abstract: The present invention provides methods for high-throughput screening for bioactive compounds, in particular those that bind to RNA sequences involved in the pathogenesis of disease or in regulation of a physiological function. The methods involve measuring the conformation of an RNA target in the presence and absence of test ligands, and identifying as a ligand any test ligand that causes a measurable change in target RNA conformation.

Abstract: A novel method for screening chemical compounds (test ligands) for potential pharmaceutical effectiveness is provided. The disclosed method identifies possible therapeutic test ligands by placing them in the presence of target proteins and determining their ability to increase or decrease the ratio of folded target protein to unfolded target protein. The present methods do not require that biochemical function of the target protein be known, nor that any other ligands be previously identified.

Abstract: The invention provides novel yeast cells comprising genes whose expression can be modulated by growth in the presence or absence of metal ions, methods for making such yeast cells, and methods of using such yeast cells for determining the requirement for expression of particular genes for the growth or viability of the yeast cells.

Abstract: Disclosed herein is a purified isolated nucleic acid encoding Candida Albicans SRB-7 (CaSRB-7) and an isolated polypeptide encoded by said nucleic acid. Also disclosed herein are vectors comprising the nucleic acid sequences, cells comprising the vectors, methods for producing the polypeptides and methods of use thereof.

Abstract: The present invention provides methods for screening for bioactive compounds, in particular those that bind to RNA sequences involved in the pathogenesis of disease or in regulation of a physiological function. The methods involve assessing the stability and/or the conformation of an RNA target in the presence and absence of test ligands, and identifying as a ligand any test ligand that causes a measurable change in target RNA stability and/or conformation. In a preferred embodiment, the effect of a ligand on target RNA stability and/or conformation is assessed by measuring the fluorescence polarization of a fluorescently labeled probe.

Abstract: The invention relates to Mycobacterium tuberculosis RNA polymerase algU sigma subunit protein, DNA encoding, and methods of detecting inhibitors of the RNA polymerase.

Abstract: The present invention provides isolated nucleic acids encoding RNA polymerase alpha subunit from M. tuberculosis, vectors comprising the nucleic acids, cells comprising the vectors, and methods for producing M. tuberculosis alpha subunit. The invention also provides in vitro and in vivo methods for high-throughput screening to identify inhibitors of M. tuberculosis RNA polymerase.

Abstract: The present invention provides methods for screening for bioactive compounds, in particular those that bind to RNA sequences involved in the pathogenesis of disease or in regulation of a physiological function. The methods involve assessing the stability and/or the conformation of an RNA target in the presence and absence of test ligands, and identifying as a ligand any test ligand that causes a measurable change in target RNA stability and/or conformation. In a preferred embodiment, the effect of a ligand on target RNA stability and/or conformation is assessed by measuring the fluorescence polarization of a fluorescently labeled probe.

Abstract: Disclosed are pharmaceutical compositions comprising aryl and heteroaryl hydrazone, hydrazine and thiosemicarbazone derivatives of formulae I and II, and methods for using the compositions as antifungal agents. The invention also relates to novel aryl and heteroaryl hydrazone, hydrazine and thiosemicarbazone derivatives of formulae I and II, their preparation, to pharmaceutical compositions containing them, and to methods of using them to alleviate fungal infections.

Abstract: Disclosed are pharmaceutical compositions and formulations comprising benzoquinoline derivatives having the formula (I) to (V), wherein formula (I) is: X is selected from the group consisting of O, S, CH2, CH2-CH2, C═O or NRB; Y is C or N; R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen, halogen, linear or branched chain lower alky, alkenyl, alkynyl, alkoxy or acyl; X-RA and R3, or R3 and R4, are optionally linked together to form a C3-C4 alkylene bridge, where X is CH2 or C═O; provided that: when X is NRB, then (a) RB is hydrogen, and RA is a linear or branched chain lower alkyl, aryl, heteroaryl, cycloalkyl or cycloalkenyl optionally interrupted by at least one heteroatom, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or cycloalkenyl being optionally substituted singly or plurally by at least one of a linear or branched chain lower alkyl, alkenyl, alkynyl, acyl, alkoxy, or cycloalkyl optionally interrupted by at least one heter

Abstract: The present invention provides convergent processes for preparing myxopyronins and corallopyronins, compounds useful as antibacterial therapeutics. The present invention also provides novel compositions of matter which are useful for the preparation of pyronin antibiotics.