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Re: Antisense drugs - Working at the Genetic Level » Neal

Posted by Cam W. on March 8, 2001, at 8:43:45

In reply to Antisense drugs - Working at the Genetic Level, posted by Neal on March 8, 2001, at 1:33:52

Neal - This research should be facinating, as long as the targeted protein (enzyme, etc) isn't vital in some chemical reaction not related to the defective pathway. - Cam


> At a recent meeting of the National Depressive and Manic-Depressive Association Conference in Boston, the speaker, Charles Nemeroff MD, PhD of Emory University, said that antisense drugs may be "the ultimate magic bullet".
>
> Antisense drugs work at the genetic level to interrupt the process by which disease-causing proteins are produced. Proteins play a central role in virtually every aspect of human metabolism. Almost all human diseases are the result of inappropriate protein production (or disordered protein performance). Antisense drugs are designed to inhibit the production of disease-causing proteins.
>
> How Antisense Drugs Work:
>
> The information necessary to produce proteins in cells is contained in genes. Specific genes contain information to produce specific proteins. The information required for the human body to produce all proteins is contained in the human genome and its collection of more than 100,000 genes. Genes are made up of DNA which contains information about when and how much of which protein to produce, depending upon what function is to be performed.
>
> The DNA molecule is a "double helix" -- a duplex of entwined strands. In each duplex, the bases or nucleotides (Adenine, Thymidine, Guanine, Cytosine) are weakly bound or "paired" by hydrogen bonds to complementary nucleotides on the other strand (A to T, G to C). Such highly specific complementary base pairing is the essence of information transfer from DNA to its intermediary, messenger RNA (mRNA), and carries the information, spelled out by the specific sequences of bases, necessary for the cell to produce a specific protein.
>
> During transcription of information from DNA into mRNA, the two complementary strands of the DNA partly uncoil. The "sense" strand separates from the "antisense" strand. The "antisense" strand of DNA is used as a template for transcribing enzymes which assemble mRNA -- a process called "transcription." Then, mRNA migrates into the cell where other cellular structures called ribosomes read the encoded information, its mRNA's base sequence, and in so doing, string together amino acids to form a specific protein. This process is called "translation."
>
> Antisense drugs are complementary strands of small segments of mRNA. To create antisense drugs, nucleotides are linked together in short chains (called oligonucleotides) Each antisense drug is designed to bind to a specific sequence of nucleotides in its mRNA target to inhibit production of the protein encoded by the target mRNA. By acting at this earlier stage in the disease-causing process to prevent the production of a disease-causing protein, antisense drugs have the potential to provide greater therapeutic benefit than traditional drugs which do not act until the disease-causing protein has already been produced.
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> Antisense drugs have the potential to be much more selective or specific than traditional drugs, and therefore more effective, because they bind to mRNA targets at multiple points of interaction at a single receptor site. Traditional drugs usually bind at only two points of interaction.
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> The design of antisense compounds also has the advantage of being less complex, more rapid and more efficient than traditional drug design directed at protein targets. Rational drug design usually begins by characterizing the three-dimensional structure of the protein target in order to design a prototype drug to interact with the target. Proteins, however, are complex molecules whose structure is difficult to predict. In contrast, antisense compounds are designed to bind to mRNA whose structures are more easily understood and predicted. Once the receptor sequence on the mRNA is identified, the three-dimensional structure of the receptor site can be defined, and the prototype antisense drugs can be designed.
>
>


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poster:Cam W. thread:55900
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