Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Patent
1993-10-06
1996-07-02
Nucker, Christine M.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
435 6, 435 23, 435 34, 435 681, 435 691, 435 692, 435184, 435244, 4352523, 435974, C12Q 170
Patent
active
055321240
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Chemotherapeutic intervention has been a bulwark of modern medicine. Treatment of cancer, hypertension, heart disease, inflammation and endocrine disorders are just a few examples of human disorders, some of them life threatening, which have been successfully managed or cured by drugs alone or in combination with other therapy. Infectious diseases caused by bacteria, fungi and parasites have also been successfully managed or cured by drug therapy.
Central to the discovery of new medically effective drugs is the ability to screen for effective agents and identify sources of their production. It is safe to say that the ability to screen and locate important compounds is often the limiting step in the discovery of these agents. Current assays for drugs used in the treatment of hypertension and inflammation, for example, often require the use of unpredictable enzyme and cellular assays. Similarly, the detection of drugs that are effective against viruses often require sophisticated and cumbersome cell culture or virus enzyme assays. These assays are not often amenable to high volume studies, and most crude samples of impure compounds or crude extracts of natural products, which are often the source of effective drugs, cannot be tested in these assays without considerable prior purification.
In addition, the discovery of effective drugs depends either upon the large scale screening of thousands of different compounds or the reasoned design of drugs that, by their structure, are predicted to be effective. This approach has been, to date, the only means of drug discovery.
Much attention has focused on the discovery of therapeutic agents effective against Human Immunodeficiency Virus (HIV). HIV is the causative agent of the human disease, Acquired Immunodeficiency Syndrome (AIDS) and AIDS Related Complex (ARC). These are devastating illnesses that represent a major worldwide health threat. HIV is a member of the RNA genome-containing retroviruses and requires the function of virally specified gag and reverse transcriptase (pol) polypeptides. As with other RNA tumor viruses, the HIV life cycle involves synthesis of a double stranded DNA copy of the genomic RNA. This process is catalyzed by the viral reverse transcriptase, and inhibition of this enzyme inhibits virus replication.
Dependency of HIV upon unique virally encoded functions, such as the reverse transcriptase, presented the possibility of rationally designing antiviral agents to be directed towards interfering with those functions. For example, the nucleotide analog azidothymidine (AZT) is an effective anti-HIV agent and is presumed to work by forming chain terminating products generated by retroviral reverse transcriptase. It should therefore be possible to impede or prevent virus growth by developing pharmacological agents that inhibit essential virus functions.
The gag and pol proteins perform essential HIV retroviral functions. Mature gag and pol products are derived from the proteolytic processing of polypeptide precursors. This proteolytic cleavage is mediated by a virally specified protease that is essential for virus growth. Inhibition of this viral protease is therefore likely to prevent HIV maturation.
There is enormous interest in the discovery of HIV protease inhibitors present as natural products or derived from chemical synthesis. Each candidate inhibitor must be tested for its ability to prevent HIV protease from enzymatically cleaving substrates such as preparations of either gag-pol precursors or synthetic oligopeptides containing the HIV protease recognition sequence. Such assays are time consuming and costly, usually involving separation of cleaved products by electrophoresis or other methods of chromatography, such as HPLC. All of these methods require a reasonable degree of technical sophistication. The search for an effective HIV protease inhibitor would be greatly assisted by the availability of a simple, rapid and inexpensive assay.
Similarly, it is critical that a rapid screening assay for inhibitors of
REFERENCES:
McCall et al, "A High Capacity Microbial Screen for Inhibitors of Human Rhinovirus Protease 3C" Biotechnology, vol. 12, (Oct. 1994), pp. 1012-1016.
Block et al "Novel Bacteriological Assay for Detection of Potential Antiviral Agents" Antimicrobiological Agents & Chemoth vol. 34, No. 12 pp. 2337-2341 (1990).
Debouck et al "Human immunodeficiency virus protease expressed in E coli exhibits autoprocessing & specific maturation of the gag precursor" PNAS vol. 84 pp. 8903-8906 (Dec. 1987).
Moore et al "Peptide Substrates & Inhibitors of the HIV-1 Protease" Biochem & Biophys Research Com vol. 159, No. 2 pp. 420-425 (Mar. 15, 1989).
Barany "Two-codon insertion mutagenesis of plasmid genes by using single-stranded hexameric oligonucleotides" PNAS vol. 82 pp. 4202-4206 (Jun. 1985).
Block Timothy M.
Grafstrom Robert H.
Nucker Christine M.
Stucker Jeffrey
Thomas Jefferson University
LandOfFree
Genetically engineered bacteria to identify and produce medicall does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Genetically engineered bacteria to identify and produce medicall, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Genetically engineered bacteria to identify and produce medicall will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1505682