Abstract: The present invention provides novel glycoluril derivatives for use as core molecules in combinatorial chemistry. Core molecules of the present invention can contain from one to six building blocks. Preferred building blocks are substituted amine radicals. Combinatorial libraries containing such core molecules are also provided.

Abstract: Disclosed are multibinding compounds which are ?2 adrenergic receptor agonists and are useful in the treatment and prevention of respiratory diseases such as asthma, bronchitis. They are also useful in the treatment of nervous system injury and premature labor.

Abstract: The invention provides optimized antisense oligonucleotides complementary to the DNA methyltransferase gene or its RNA transcript. The invention further provides methods for using such antisense oligonucleotides as analytical and diagnostic tools, as potentiators of transgenic plant and animal studies and gene therapy approaches, and as potential therapeutic agents.

Abstract: Novel vectors are disclosed for expressing and secreting heterologous polypeptides from filamentous fungi. Such vectors are used in novel processes to express and secrete such heterologous polypeptides. The vectors used for transforming a filamentous fungus to express and secrete a heterologous polypeptide include a DNA sequence encoding a heterologous polypeptide and a DNA sequence encoding a signal sequence which is functional in a secretory system in a given filamentous fungus and which is operably linked to the sequence encoding the heterologous polypeptide. Such signal sequences may be the signal sequence normally associated with the heterologous polypeptides or may be derived from other sources. The vector may also contain DNA sequences encoding a promoter sequence which is functionally recognized by the filamentous fungus and which is operably linked to the DNA sequence encoding the signal sequence.

Abstract: A method for preparing a CDNA from a mRNA using a reverse transcriptase wherein reverse transcription is performed at a temperature at which the mRNA does not take a secondary structure, for example, at a temperature of 45° C. or more. The method is performed, for example, using a heat-labile reverse transcriptase in the presence of a substance exhibiting chaperone function having chaperone function such as saccharides. The method is performed, for example, in the presence of metal ions necessary for activation of the reverse transcriptase and a chelating agent for the metal ions such as a deoxynucleotide triphosphate. The method is capable of reverse transcription over the full length of mRNA template even if the mRNA is a long chain mRNA and, as a result, producing a full length cDNA.

Abstract: Modified tRNA molecules are provided which inhibit HIV-1 replication. A tRNA molecule has a modified aminoacyl acceptor stem with a 3′ segment which has reduced complementarity to the HIV primer binding site can initiate aberrant reverse transcription and/or interfere with reverse transcription. tRNA molecules which are modified in regions outside the acceptor stem which interact with reverse trancriptase or the HIV-1 RNA template can also inhibit HIV-1 replication. Methods are disclosed for introducing the modified tRNA molecules into human cells.

Abstract: The invention provides a method of tracking, identifying, and/or sorting classes or subpopulations of molecules by the use of oligonucleotide tags. Oligonucleotide tags of the invention comprise oligonucleotides selected from a minimally cross-hybridizing set. Preferably, such oligonucleotides each consist of a plurality of subunits 3 to 9 nucleotides in length. A subunit of a minimally cross-hybridizing set forms a duplex or triplex having two or more mismatches with the complement of any other subunit of the same set. The number of oligonucleotide tags available in a particular embodiment depends on the number of subunits per tag and on the length of the subunit. An important aspect of the invention is the use of the oligonucleotide tags for sorting polynucleotides by specifically hybridizing tags attached to the polynucleotides to their complements on solid phase supports.

Abstract: The invention relates to a method for producing human cell lines and cell and cell-lines produced by such a method. The method comprising the use of precursor or undifferentiated cells treated with an immortalising agent which is susceptible to environmental conditions so as to provide for selective activation/deactivation of said immortalising agent and so selective activation of differentiation.

Abstract: Compositions and methods are provided for the treatment and diagnosis of diseases associated with the expression of one or more of the &bgr;I, &bgr;II, &ggr;, &dgr;, &egr;, &zgr; or &eegr; isoforms (isozymes) of protein kinase C (PKC). Oligonucleotides are provided which are targeted to nucleic acids encoding PKC-&bgr;I, PKC-&bgr;II, PKC-&ggr;, PKC-&dgr;, PKC-&egr;, PKC-&zgr; or PKC-&eegr;. Provided herein are oligonucleotides specifically hybridizable with a translation initiation site, 5′-untranslated region, 3′-untranslated region or other targeted region of a &bgr;I, &bgr;II, &ggr;, &dgr;, &egr;, &zgr; or &eegr; isoform of PKC, wherein at least about 75% of the nucleoside units of a given oligonucleotide are joined together by a stereospecific (i.e., Sp or Rp) phosphorothioate 3′ to 5′ linkages. In preferred embodiments, the oligonucleotides of the disclosure additionally contain one or more chemical modifications.

Abstract: The invention relates to a gene transfer system binding to a growth factor receptor, comprising 4-element complex gene transfer system consisting of ligand oligopeptide/polycationic polypeptide/endosome release oligopeptide/exogenous DNA or 3-element complex consisting of ligand oligopeptide/polycationic polypeptide/exogenous DNA. The invention exemplifies E5, GE7, GV1 and GV2 systems and they can be targeted for the introduction of exogenous genes into malignant tumor cells or tumor vascular endotheliocytes. They are also able to highly inhibit the growth of tumor cells in animals while p15, p16 or p21WAF−1 was used as exogenous genes. The system according to the invention is a new introduction system in tumor gene therapy.

Abstract: The invention discloses methods and materials for the utilization of chemically modified oligonucleotides in the treatment of drug-resistant bacterial infections including drug-resistant tuberculosis.

Abstract: An antiretroviral composition for inhibiting the action of reverse transcriptase include a nucleoside analog containing a six-carbon levo hexose sugar, for example, L-rhamnose or L-fucose. Treatment is achieved by delivering the antiretroviral to the infected system, wherein the reverse transcription process is inhibited via steric hindrance, halting the viral RNA replication. Delivery may be accomplished by conventional methods, such as via oral dosing or injection. Additional delivery methods are also contemplated, including packaging in liposomes and protein targeting. The composition and method are also useful for inhibiting the proliferation of cancer cells by halting the transcription process.

Abstract: Retroviral vectors for producing coordinately expressed polycistronic mRNA in transfected host cells. A representative retroviral construct capable of forming a proviral genome in a host cell contains a first nucleotide coding sequence, a second nucleotide coding sequence, and a third nucleotide sequence capable of hybridizing under stringent conditions to a 5′ nontranslated region (NTR) of a picornavirus RNA or its complementary RNA strand. The first, second, and third nucleotide sequences are operably linked such that transcription of the proviral genome gives rise to a messenger RNA molecule containing transcripts of the first, second, and third nucleotide sequences. The transcript of the third nucleotide sequence in the messenger RNA molecule contains a nucleic acid capable of forming a regulatory stem-loop nucleic acid structure followed by at least one operable AUG start codon.

Abstract: This invention relates to products and methods for treating cancer and for diagnosing tumorigenicity and other diseases associated with alteration in GP88 expression or action. Antagonists to an 88 KDa autocrine growth and tumorigenicity stimulator are provided which inhibit its expression or biological activity. The antagonists include antisense oligonucleotides and antibodies.

Abstract: A novel insertion sequence, which has been found in the sMMO gene coding for methane monooxygenase of methane-assimilating bacterium Methylococcus capsulatus NCIMB 11132 strain, and has inverted repeat sequences consisting of a sequence of the nucleotide numbers 5-19 of SEQ ID NO: 1 at the both ends, can be utilized as effective means for genetic analysis including creation of insertion mutant strains, gene mapping, promoter searching, insertion of genetic information into chromosomal DNA, disruption of specific gene and the like, or utilized for improving methane-assimilating bacteria by chromosomal genetic engineering techniques.

Abstract: The invention describes sdp3.8 tumor associated nucleic acids, including fragments and biologically functional variants thereof. Also included are polypeptides and fragments thereof encoded by such nucleic acids, and antibodies relating thereto. Methods and products also are provided for diagnosing and treating conditions characterized by expression of a sdp3.8 gene product.

Abstract: The present invention relates to ubiquitin-specific thiol proteases or deubiquitinating enzymes, referred to as DUB (DeUBiquitinating) enzymes, of eukaryotic origin which are members of a superfamily of deubiquitinating enzymes and which comprise a new subfamily of deubiquitinating enzymes which are similar in size and amino acid sequence to one another. DUB enzymes of the present invention are of eukaryotic origin, such as vertebrate origin, including mammalian (e.g., murine, human) origin, as well as yeast origin. All DUB enzymes of the present invention are inducible by at least one cytokine.

Abstract: The invention provides a method of tracking, identifying, and/or sorting classes or subpopulations of molecules by the use of oligonucleotide tags. Oligonucleotide tags of the invention comprise oligonucleotides selected from a minimally cross-hybridizing set. Preferably, such oligonucleotides each consist of a plurality of subunits 3 to 9 nucleotides in length. A subunit of a minimally cross-hybridizing set forms a duplex or triplex having two or more mismatches with the complement of any other subunit of the same set. The number of oligonucleotide tags available in a particular embodiment depends on the number of subunits per tag and on the length of the subunit. An important aspect of the invention is the use of the oligonucleotide tags for sorting polynucleotides by specifically hybridizing tags attached to the polynucleotides to their complements on solid phase supports.

Abstract: The invention includes novel fusion nucleic acids encoding fusion polypeptides which when expressed in a filamentous fungus result in the expression of fusion polypeptides. The fusion nucleic acids comprise four nucleic acids which encode a fusion polypeptide comprising first, second, third and fourth amino acid sequences. The first nucleic acid encodes a signal polypeptide functional as a secretory sequence in a first filamentous fungus. The second nucleic acid encodes a secreted polypeptide or functional portion thereof which is normally secreted from the same filamentous fungus or a second filamentous fungus. The third nucleic acid encodes a cleavable linker while the fourth nucleic acid comprises at least two nucleic acids encoding desired polypeptides.

Abstract: Disclosed are oligonucleotide compounds that inhibit the expression of angiogenin when administered to a mammal. Also disclosed are methods and pharmaceutical compositions for inhibiting the expression of angiogenin useful in therapy or diagnosis.