Abstract: Disclosed are systems and methods for high throughput screening to detect translation readthrough induced drugs (TRID). The systems use highly purified, eukaryotic cell-free protein synthesis systems that distinguish TRIDs acting directly on the protein synthesis machinery from those that act indirectly.

Abstract: Provided are methods for labeling transfer RNA comprising replacing the uracil component of a dihydrouridine of said transfer RNA with a fluorophore. The disclosed methods may comprise fluorescent labeling of natural tRNAs (i.e., tRNAs that have been synthesized in a cell, for example, in a bacterium, a yeast cell, or a vertebrate cell) at dihydrouridine (D) positions, or fluorescent labeling of synthetic tRNAs. In another aspect, the present invention provides methods for assessing protein synthesis in a translation system comprise providing a tRNA having a fluorophore substitution for the uracil component of a dihydrouridine in a D loop of the tRNA; introducing the labeled tRNA into the translation system; irradiating the translation system with electromagnetic radiation, thereby generating a fluorescence signal from the fluorophore; detecting the fluorescence signal; and, correlating the fluorescence signal to one or more characteristics of the protein synthesis in the translation system.

Abstract: Provided are methods for labeling transfer RNA comprising replacing the uracil component of a dihydrouridine of said transfer RNA with a fluorophore. The disclosed methods may comprise fluorescent labeling of natural tRNAs (i.e., tRNAs that have been synthesized in a cell, for example, in a bacterium, a yeast cell, or a vertebrate cell) at dihydrouridine (D) positions, or fluorescent labeling of synthetic tRNAs. In another aspect, the present invention provides methods for assessing protein synthesis in a translation system comprise providing a tRNA having a fluorophore substitution for the uracil component of a dihydrouridine in a D loop of the tRNA; introducing the labeled tRNA into the translation system; irradiating the translation system with electromagnetic radiation, thereby generating a fluorescence signal from the fluorophore; detecting the fluorescence signal; and, correlating the fluorescence signal to one or more characteristics of the protein synthesis in the translation system.

Abstract: Provided are methods for labeling transfer RNA comprising replacing the uracil component of a dihydrouridine of said transfer RNA with a fluorophore. The disclosed methods may comprise fluorescent labeling of natural tRNAs (i.e., tRNAs that have been synthesized in a cell, for example, in a bacterium, a yeast cell, or a vertebrate cell) at dihydrouridine (D) positions, or fluorescent labeling of synthetic tRNAs. In another aspect, the present invention provides methods for assessing protein synthesis in a translation system comprise providing a tRNA having a fluorophore substitution for the uracil component of a dihydrouridine in a D loop of the tRNA; introducing the labeled tRNA into the translation system; irradiating the translation system with electromagnetic radiation, thereby generating a fluorescence signal from the fluorophore; detecting the fluorescence signal; and, correlating the fluorescence signal to one or more characteristics of the protein synthesis in the translation system.

Abstract: Provided are methods for labeling transfer RNA comprising replacing the uracil component of a dihydrouridine of said transfer RNA with a fluorophore. The disclosed methods may comprise fluorescent labeling of natural tRNAs (i.e., tRNAs that have been synthesized in a cell, for example, in a bacterium, a yeast cell, or a vertebrate cell) at dihydrouridine (D) positions, or fluorescent labeling of synthetic tRNAs. In another aspect, the present invention provides methods for assessing protein synthesis in a translation system comprise providing a tRNA having a fluorophore substitution for the uracil component of a dihydrouridine in a D loop of the tRNA; introducing the labeled tRNA into the translation system; irradiating the translation system with electromagnetic radiation, thereby generating a fluorescence signal from the fluorophore; detecting the fluorescence signal; and, correlating the fluorescence signal to one or more characteristics of the protein synthesis in the translation system.

Abstract: Provided are methods for labeling transfer RNA comprising replacing the uracil component of a dihydrouridine of said transfer RNA with a fluorophore. The disclosed methods may comprise fluorescent labeling of natural tRNAs (i.e., tRNAs that have been synthesized in a cell, for example, in a bacterium, a yeast cell, or a vertebrate cell) at dihydrouridine (D) positions, or fluorescent labeling of synthetic tRNAs. In another aspect, the present invention provides methods for assessing protein synthesis in a translation system comprise providing a tRNA having a fluorophore substitution for the uracil component of a dihydrouridine in a D loop of the tRNA; introducing the labeled tRNA into the translation system; irradiating the translation system with electromagnetic radiation, thereby generating a fluorescence signal from the fluorophore; detecting the fluorescence signal; and, correlating the fluorescence signal to one or more characteristics of the protein synthesis in the translation system.

Abstract: The present invention relates to systems and methods for measuring the rate of translation of a target protein in cells, which are based on the detection of translation of one or more predetermined codon pairs during synthesis of the target protein. The detection is provided by a FRET signal emitted from labeled tRNA molecules which are juxtaposed during synthesis of the protein.

Abstract: The present invention relates to systems and methods for measuring the rate of translation of a target protein in cells, which are based on the detection of translation of one or more predetermined codon pairs during synthesis of the target protein. The detection is provided by a FRET signal emitted from labeled tRNA molecules which are juxtaposed during synthesis of the protein.

Abstract: Provided are methods for labeling transfer RNA comprising replacing the uracil component of a dihydrouridine of said transfer RNA with a fluorophore. The disclosed methods may comprise fluorescent labeling of natural tRNAs (i.e., tRNAs that have been synthesized in a cell, for example, in a bacterium, a yeast cell, or a vertebrate cell) at dihydrouridine (D) positions, or fluorescent labeling of synthetic tRNAs. In another aspect, the present invention provides methods for assessing protein synthesis in a translation system comprise providing a tRNA having a fluorophore substitution for the uracil component of a dihydrouridine in a D loop of the tRNA; introducing the labeled tRNA into the translation system; irradiating the translation system with electromagnetic radiation, thereby generating a fluorescence signal from the fluorophore; detecting the fluorescence signal; and, correlating the fluorescence signal to one or more characteristics of the protein synthesis in the translation system.

Abstract: Provided are methods for labeling transfer RNA comprising replacing the uracil component of a dihydrouridine of said transfer RNA with a fluorophore. The disclosed methods may comprise fluorescent labeling of natural tRNAs (i.e., tRNAs that have been synthesized in a cell, for example, in a bacterium, a yeast cell, or a vertebrate cell) at dihydrouridine (D) positions, or fluorescent labeling of synthetic tRNAs. In another aspect, the present invention provides methods for assessing protein synthesis in a translation system comprise providing a tRNA having a fluorophore substitution for the uracil component of a dihydrouridine in a D loop of the tRNA; introducing the labeled tRNA into the translation system; irradiating the translation system with electromagnetic radiation, thereby generating a fluorescence signal from the fluorophore; detecting the fluorescence signal; and, correlating the fluorescence signal to one or more characteristics of the protein synthesis in the translation system.

Abstract: The present invention relates to systems and methods for measuring the rate of translation of a target protein in cells, which are based on the detection of translation of one or more predetermined codon pairs during synthesis of the target protein. The detection is provided by a FRET signal emitted from labeled tRNA molecules which are juxtaposed during synthesis of the protein.

Abstract: Provided are methods for labeling transfer RNA comprising replacing the uracil component of a dihydrouridine of said transfer RNA with a fluorophore. The disclosed methods may comprise fluorescent labeling of natural tRNAs (i.e., tRNAs that have been synthesized in a cell, for example, in a bacterium, a yeast cell, or a vertebrate cell) at dihydrouridine (D) positions, or fluorescent labeling of synthetic tRNAs. In another aspect, the present invention provides methods for assessing protein synthesis in a translation system comprise providing a tRNA having a fluorophore substitution for the uracil component of a dihydrouridine in a D loop of the tRNA; introducing the labeled tRNA into the translation system; irradiating the translation system with electromagnetic radiation, thereby generating a fluorescence signal from the fluorophore; detecting the fluorescence signal; and, correlating the fluorescence signal to one or more characteristics of the protein synthesis in the translation system.

Abstract: The invention relates to compositions which are useful for inhibiting ribonucleotide reductase enzymes, including the mammalian ribonucleotide reductase enzyme. The compositions include, but are not limited to, linear peptides, cyclic peptides, peptide analogs, and peptidomimetics. Methods of using the compositions of the invention to treat cancer and viral and bacterial infections are disclosed.

Abstract: The invention provides analogues of .alpha.-1-antichymotrypsin having amino acid substitutions at position 358. .alpha.-1-antichymotrypsin analogues having amino acid substitutions at positions 356-361 and analogues having amino acid substitutions at positions 356-361 wherein the amino acid at position 358 is substituted are also within the scope of the invention. These analogues exhibit chymase inhibitory activity. Also provided are novel .alpha.-1-antichymotrypsins having an N-terminal extension of methionine-alanine-serine or alanine-serine. Expression vectors for the production of .alpha.-1-antichymotrypsins are also provided. The present invention also provides host cells and cell cultures capable of expressing analogues of .alpha.-1-antichymotrypsin, as well as protein preparations from the host cells. Methods of producing and using the analogues of .alpha.-1-antichymotrypsin to inhibit chymase activity are also provided.

Abstract: The present invention provides an analogue of human .alpha.-1-antichymotrypsin wherein the amino acid at position 358 is selected from the group consisting of isoleucine, valine, alanine, aspattic acid, threonine, and glutamic acid.

Abstract: This invention relates to the ribonucleotide reductase of Plasmodium falciparum (Pf RR), to the subunits of Pf RR (Pf R1 and Pf R2), and to compounds comprising peptides derived from the Pf R2 C-terminus sequence that inhibit the action of protozoal RR. The invention provides a method for the prevention and treatment of malaria caused by P. falciparum by controlling the proliferation of P. falciparum comprising administering to a patient at least one peptide according to the invention. Antimalarial compositions are provided which comprise a pharmaceutically acceptable carrier and at least one peptide according to the invention which inhibits the P. falciparum ribonucleotide reductase reduction of ribonucleotides to 2'-deoxyribonucleotides. Also provided are methods for diagnosing malaria and for screening potential antimalarial agents.

Abstract: The invention provides .alpha.-1-antichymotrypsin and protein preparations comprising human .alpha.-1-antichymotrypsin produced by E. coli cells transformed with a DNA sequence encoding human .alpha.-1-antichymotrypsin. The invention also provides methods for producing .alpha.-1-antichymotrypsin. The invention further provides analogues of .alpha.-1-antichymotrypsin that exhibit antichymotrypsin, anti-trypsin and anti-thrombin activity and methods of producing the analogues.

Abstract: The invention provides .alpha.-1-antichymotrypsin and protein preparations comprising human .alpha.-1-antichymotrypsin produced by E. coli cells transformed with a DNA sequence encoding human .alpha.-1-antichymotrypsin. The invention also provides methods for producing .alpha.-1-antichymotrypsin. The invention further provides analogues of .alpha.-1-antichymotrypsin that exhibit antichymotrypsin, anti-trypsin and anti-thrombin activity and methods of producing the analogues.