Term Paper on "Genome Project on Drug Design and Discovery"

Term Paper 4 pages (1163 words) Sources: 1+

[EXCERPT] . . . .

Genome Project on Drug Design and Discovery

The advances that have been made due to the mapping of the human genome are substantial and along with this are substantial advances in medicine and most specifically in pharmacology. It was reported recently that "a further human homolog of ACE, referred to as ACE 2, was identified and shown to be an essential regulator of cardiac function. It differs from ACE in that it contains a sing zinc-binding catalytic domain, is a carboxypeptidase with preference for carboxy-terminal hydrophic or basic residues, and is not affected by ACE inhibitors." (Riordan, 2003) These ACE inhibitors are now the chosen treatment for treatment of hypertension and congestive heart failure, left ventricular systolic dysfunction and myocardial infarction.

SEARCHING THE PUBLIC GENOME DATABASE

Time Asia reports that "sifting through the human genome for therapeutically useful gems...requires a well-designed search strategy combined with powerful technology. At Millennium, housed in a factory that once stamped out heart shaped candy boxes for Valentines' Day, that strategy is embodied in Zeus, whose job is to find the handful of genes among the genome's tens of thousands that are key to individual diseases and thus key to making effective medications." (Lemonick, 2001)

II. USING MICROASSAYS TO NARROW THE OPTIONS

In 1998 a team used the reasoning of other drug companies who have "often found new medicines by seeking compounds similar to ones they already know, and since most pharmacologically active compounds are based on proteins" or in actuality "chemicals manufactured naturally from genetic instructions" to attempt improvement on the drugs used for lower blood-pressure which are known as 'ace inhibitors'. The researches went to work and "plugged in some genetic sequences found in the gene for ace and came up with 10,000 genes that might have comparable activity." (Lemonick, 2001) Then Zeus was used in the initiative of setting up microarray analyses "and winnowed the 10,000 down to one promising protein they call ace-2." (Lemonick, 2001) Stated in a separate article entitled: "DNA Microarrays: The Workhorse of Genomic Medicine" is the explanation of the use of Microarrays. Stated is that: "Microarrays detect active genes by exploiting the fact that when the two strands of a gene in the double-stranded DNA molecule are separated, each can readily pick its partner out of a crowd of similar molecules." (Kher, 2001)

III. IDENTIFYING AND ISOLATING THE DRUGS

Stated in the Time Asia publication is that: "Testing the enzyme on tissue cells from different organs in the body, the scientists showed that whereas the original ace acts broadly on many tissues in the body, ace-2 is particularly active in heart and kidney cells, where it might be more effective in controlling high blood pressure." (Lemonick, 2001) Since the team was already knowledgeable of how ace worked on the molecular level they knew which test to use to determine whether the same effects came from ace-2 and it was found that it did.

IV. TESTING ON ANIMALS

The research team and scientists worked their way through Millennium's library that contained: "700 different classes of compounds for molecules whose chemistry made them candidates to clamp down on ace-2 activity. Then, with the help of protein-modeling software they manipulated the chemical structure of their new inhibitor to give it optimal binding affinity with the ace-2 receptor. In about two years, Millennium had created a new blood-pressure-drug candidate that is now being tested in animals." (Lemonick, 2001) This team and their technology had accomplished in a mere two years… READ MORE

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