Abstract: Herein are described the preparation of a series of synthetic rocaglates, amidino- and amino-rocaglates, which display inhibition of protein translation and tumor cell proliferation (in vitro and in vivo). The methods described herein allow the preparation of libraries of modified rocaglates. This chemical modification of the rocaglate scaffold changes the C8b-hydroxyl of the natural product series to a more optimal hydrogen bond donor/acceptor.

Abstract: The present invention relates to a anti-proliferative target for designing chemotherapeutic agents, which comprises a EIF4A protein having an amino acid sequence, as defined in claim 1.

Abstract: The invention provides novel inhibitors of protein translation initiation and inhibitors of eIF4F activity that can increase chemosensitivity or diminish or reverse chemoresistance in growth transformed cells and thereby reduce hyperproliferative conditions, such as cancer progression, in select patient populations having particular tumor genotypes. The invention also provides methods which target translation initiation controls in growth-transformed cells, such as tumor subtypes with altered expression of a gene activity, including the human akt, bcl-2, eIF4E, eIF4A or PTEN activities, to restore drug sensitivity in vivo in a genotype selective manner. In one aspect, the inhibitors of translation initiation of the invention are rocaglates, i.e., cyclopenta[b]benzofurons, which increases chemosensitivity or diminishes or reverses chemoresistance either alone or in combination, additively or synergistically, with other agents that alter growth or death.

Abstract: The present invention relates to a anti-proliferative target for designing chemotherapeutic agents, which comprises a EIF4A protein having an amino acid sequence, as defined in claim 1.

Abstract: The invention relates to bacterial genes and proteins that are implicated in the process of DNA replication and also to bacteriophage genes and their protein products that interact with bacterial proteins involved in DNA replication. More particularly, the invention relates to compositions and methods involving an essential Staphylococcus aureus gene and its encoded protein STAAU_R9. In addition, the invention relates to screening assays to identify compounds which modulate the level and/or activity of STAAU_R9 and to such compounds.

Abstract: A method for identifying suitable targets for antibacterial agents based on identifying targets of bacteriophage-encoded proteins is described. Also described are compositions useful in the identification methods and in inhibiting bacterial growth, and methods for preparing and using such compositions.

Abstract: The invention provides the components of in vivo and in vitro systems and methods which use them to study the effects of altered expression of a gene activity, such as the human akt, bcl-2, eIF4E or PTEN activities, on the descendants of stem cells that have been engineered to give rise to hematopoietic tumorigenic or tumor cells, such as lymphomas, with a high frequency. The present invention provides vectors, cells and mammals, and methods which in part depend on such products, useful for understanding tumorigenesis and its treatments, and in particular, for identifying and studying inhibitors and activators associated with tumor cell growth and growth inhibition, cell death through apoptotic pathways, and changes in apoptotic pathway components that affect drug sensitivity and resistance in tumorigenic cells.

Abstract: This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, the invention relates to polynucleotides and polypeptides of a Staphylococcus aureus (S. aureus) DnaI related protein, as well as its variants. The invention also relates to a specific interaction between the S. aureus DnaI related protein or specific regions thereof, and a growth-inhibitory protein encoded by the S. aureus bacteriophage 77 genome. The phage open reading frame (ORF) product interacts with amino acids 150–313 of S. aureus DnaI polypeptide, and the invention relates to the use of this interaction target site as the basis of drug screening assays. Accordingly, the invention provides a method for the inhibition of bacterial growth, and the treatment of bacterial infection via the inhibition of DnaI.

Abstract: The disclosure concerns particular bacteriophage open reading frame, and portions and products of those open reading frames which have antimicrobial activity. Methods of using such products are also described.

Abstract: A method for identifying suitable targets for antibacterial agents based on identifying targets of bacteriophage-encoded proteins is described. Also described are compositions useful in the identification methods and in inhibiting bacterial growth, and methods for preparing and using such compositions.

Abstract: The present invention discloses inhibitors of the primary sigma factor in Staphylococcus aureus (&sgr;SA), an essential protein implicated in RNA synthesis. The invention also discloses methods for inhibiting bacterial growth by contacting a bacterium with an antibacterial compound that specifically binds to a bacteriophage polypeptide binding domain of the Staphylococcus aureus primary sigma factor. Examples of inhibitors include bacteriophage polypeptides inhibiting growth of S. aureus and bacteriophage polypeptides binding specifically to S. aureus primary sigma factor. In addition, the invention discloses screening methods for identifying compounds which inhibit biochemical and/or cellular activity of S. aureus primary sigma factor.

Abstract: This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, the invention relates to specific interaction between the S. aureus STAAU_R2 related protein or specific regions thereof, and growth-inhibitory proteins encoded by the S. aureus bacteriophage genome. The invention relates to the use of these interaction target sites as the basis of drug screening assays.

Abstract: The disclosure concerns particular bacteriophage open reading frames, and portions and products of those open reading frames which have antimicrobial activity. Methods of using such products are also described.

Abstract: The disclosure concerns particular bacteriophage open reading frame, and portions and products of those open reading frames which have antimicrobial activity Also disclosed is an S. aureus protein that interacts with an inhibitory phage protein. Methods of using such products are also described.

Abstract: The disclosure concerns particular bacteriophage open reading frames, and portions and products of those open reading frames which have antimicrobial activity. Methods of using such products are also described.

Abstract: The invention relates to bacterial genes and proteins that are implicated in the process of DNA replication and also to bacteriophage genes and their protein products that interact with bacterial proteins involved in DNA replication. More particularly, the invention relates to compositions and methods involving an essential Staphylococcus aureus gene and its encoded protein STAAU_R9. In addition, the invention relates to screening assays to identify compounds which modulate the level and/or activity of STAAU_R9 and to such compounds.

Abstract: The Wilms' tumor gene associated with 11p3 locus on the human chromosome, as well as a method of analyzing cells for the gene is described and characterized. The gene encodes a transcription unit approximately 50 kb in size and a mRNA of approximately 3 kb, which is expressed in predominantly in kidney and gonadal tissue. The gene is alternative spliced producing four very similar mRNA transcripts. The polypeptides encoded by the Wilms' tumor DNA includes four “zinc fingers” and a region rich in proline and glutamine, suggesting that the polypeptide has a role in transcription regulation.

Abstract: The present invention relates to genetic engineering, and especially to cDNA synthesis and cDNA cloning. More specifically, a method is presented for increasing the processivity of a DNA- or RNA-dependent RNA- or DNA-polymerase comprising an addition of a general nucleic acid binding protein. In particular, the present invention relates to methods for increasing the processivity of reverse transcriptase (RT) E. coli DNA polymerase and T7 DNA polymerase using a nucleic acid binding protein such as Ncp7, recA, SSB and T4gp32. The invention further relates to assays to identify and select agents capable of increasing the processivity of a DNA or RNA-dependent polymerase, such as MMTV RT, AMV RT, T7 DNA polymerase and E-coli DNA polymerase. In a particularly preferred embodiment, the invention relates to a method for increasing the generation of full-length cDNA clones using a nucleic acid binding protein such as Ncp7, recA, SSB and T4gp32.

Abstract: The Wilms' tumor gene associated with 11p3 locus on the human chromosome, as well as a method of analyzing cells for the gene is described and characterized. The gene encodes a transcription unit approximately 50 kb in size and a mRNA of approximately 3 kb, which is expressed in predominantly in kidney and gonadal tissue. The gene is alternative spliced producing four very similar mRNA transcripts. The polypeptides encoded by the Wilms' tumor DNA includes four “zinc fingers” and a region rich in proline and glutamine, suggesting that the polypeptide has a role in transcription regulation.

Abstract: This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, the invention relates to polynucleotides and polypeptides of a Staphylococcus aureus (S. aureus) DnaI related protein, as well as its variants, hereinafter referred to as “S. aureus DnaI”, “S. aureus DnaI polypeptide(s)”, and “S. aureus dnaI polynucleotides” as the case may be. Also, the invention relates to a specific interaction between the S. aureus DnaI related protein and a growth-inhibitory protein encoded by the S. aureus bacteriophage 77 genome. The phage ORF product interacts with the S. aureus DnaI polypeptide, and the invention contemplates use of this interaction target site for the basis of a drug screening assay. In addition, the invention relates to polynucleotides and polypeptides of a protein complex containing S.