A more attractive approach to telomerase regulation would involve the regulation of human telomerase by modulating the expression ofthe protein subunits ofthe enzyme, preferably the reverse transcriptase hTERT subunit. Li et al, , The Lancet, , , describe the quantitation of angiogenic peptides bFGF in the cerebrospinal fluid of children with brain tumors. The preferred substituent s of aryl groups are halogen, trihalomethyl, hydroxyl, SH, OH, cyano, alkoxy, alkyl, alkenyl, alkynyl, and amino groups. Figure 27 is a diagram of “no-ribo” class LI ribozymes. Such nucleic acid molecules are also useful for diagnostic uses.
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C,Nature, There is no evidence that HBsAg positive food handlers pose a health risk in an occupational setting, nor should they be excluded from work. The sequences ofthe chemically synthesized ribozymes and antisense constructs used in this study are shown below in Table InD’Amico et al. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, dc-4310 Remington’s Pharmaceutical Sciences, Mack Publishing Co.
Non-dividing cells in culture have no detectable levels ofthe kDa MetAP-2 protein by immunoassay. Alzheimer’s patients, there exists an unmet need in the comprehensive treatment and prevention of this disease.
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The term also includes alkenyl groups which are unsaturated hydrocarbon groups containing at least one carbon-carbon double bond, including straight-chain, branched-chain, and cyclic groups.
If Loop II is present it is greater than or equal to three nucleotides, preferably four nucleotides. Ribozymes and antisense constructs were designed to anneal to various sites in the RNA message.
Some ofthe non-limiting examples of base modifications that can be introduced into nucleic acid molecules include, inosine, purine, pyridinone, pyridinone, phenyl, pseudouracil, 2, 4, 6-trimethoxy benzene, 3- methyl uracil, dihydrouridine, naphthyl, aminophenyl, 5-alkylcytidines e.
Once inside, the genome is translocated to the nucleus where it is repaired and cyclized. Varying binding arm lengths can be chosen to optimize activity. H refers to bases A, U, or C.
Pharmacol, 40, describe the regulation of sarcoplasmic reticulum protein phosphorylation by localized cyclic GMP- dependent protein kinase in vascular smooth muscle cells.
Insulin stimulated receptor autophosphorylation and insulin receptor substrate 1 tyrosine phosphorylation are increased dramatically as well through PTP-IB inhibition Ahmad, F.
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Furthermore, transient expression of hTERT in normal diploid human cells restored telomerase activity, demonstrating that hTERT is the only component necessary to restore telomerase activity in normal human cells Weinrich, S.
Human methionine aminopeptidase- 1, MetAP-1, accession No. By “comprising” is meant including, but not limited to, whatever follows the word “comprising”.
Injection of nude mice with cells expressing these oncogenes and hTERT resulted in rapid growth of tumors. Helix 1, 4 and 5 can be of any length; Helix 2 is between 3 and 8 base-pairs long; Y is a pyrimidine; Helix 2 H2 is provided with a least 4 base pairs i. By “stably interact” is meant, interaction ofthe oligonucleotides with target nucleic acid e.
Preferably, the alkyl group has 1 to 12 carbons. The efficacy ofthe above mentioned treatment strategies is limited.
The ribozyme and antisense construct sequences listed in Tables33, 34, icxm, 56, 58, 59, 62, 63 maybe formed of ribonucleotides or other nucleotides or non-nucleotides. In a non-limiting example, small scale syntheses are conducted on a Applied Biosystems, Inc. The use of affinity chromatography with a fumagillin-biotin conjugate resulted in the isolation of a kDa mammalian protein through covalent interaction with the bound subsfrate.
The cap may be present at the 5′-terminus 5′-cap or at the 3′-terminal 3′- cap or may be present on both termini.
In addition, hybridization probes and primers are described as inhibitors of telomerase gene function. Cardiol, 83, 89HH, describe a fransgenic rat model for the study of altered expression of calcium regulatory proteins, including phospholamban, and their effect on myocyte contractile response.
The nucleic acid molecules ofthe present invention may also be administered to a patient in combination with other therapeutic compounds to increase the overall therapeutic effect. This pool of active molecules may also contain some molecules that are not active to cleave the target inactive molecules but have dissociated from the column.
Cooperative enzyme classes regulate protein tyrosine phosphorylation and dephosphorylation events. Carbocyclic aryl groups are groups wherein the ring atoms on the aromatic ring are all carbon atoms. A complete response HBV.
Determination of binding free energies for nucleic acid molecules is well known in the art see, e. Ocam “G-cleaver” motif is meant, an enzymatic nucleic acid molecule comprising a motif as described in Eckstein et al, International PCT publication No.