| Chiralgen, Ltd. |
| Date of Establishment: |
18, March, 2008 |
| Location (Laboratory): |
Tokatsu Techno Plaza 601, 5-4-6, Kashiwanoha Kashiwa-shi, Chiba, Japan |
| Stock Capital: |
76.3 million yen |
| Capital Formation: |
SNBL 95%
Other 5% |
| President: |
Ken Takanashi |
| R&D (Outline): |
Development of stereocontorolled synthesis of phosphorous atom modified nucleic acids and novel nucleic acid medicine |
Artificial Nucleic Acids Working as Medicine:Synthesize "Left Hand"
and "Right Hand", Respectively
Based on recent research, it has come to be understood that relatively
small RNA molecules inhibit gene expression in vivo, and there is considerable
anticipation that they can be made use of medically. We aim to create high-caliber
nucleic acid drugs that are not easily degradated by enzymes by modifying
DNA and RNA phosphorus atoms.
Inhibition of Gene Expression by Nucleic Acid Drugs
Artificial nucleic acids (nucleic acid drugs) which bind to targets such
as DNA and RNA inhibit gene expression by blocking transcription and translation
mechanisms.
 (*1)
Inhibition of Gene Expression by Nucleic Acid Drugs
When DNA and RNA phosphorus atoms are modified they become asymmetrical,
and "left hand" and "right hand" stereoisomers are
the consequence (see figure). In general, the "left hand" and
"right hand" stereoisomers differ greatly in their physiochemical
properties and bioactivity.
Conformation of Phosphorothioate DNA
It is well known that phosphorothioate DNA(*2) indicate different physiological activities between the stereoisomers.
However, there is little report on the practical synthetic method for the
stereoregurated phosphorus atom modified (P-modified) nucleic acids. Development
of stereocontrolled synthesis of P-modified nucleic acids is one of the
main themes of Chiralgen, Ltd.(*3)
| Glossary |
| (*1) |
Decoy nucleic acid: Natural or synthetic oligonucleotides that bind transcriptional
factor, and inhibit gene transcription.
Antigene nucleic acid: Natural or synthetic oligonucleotides which hybridize
to the target DNA double strand, and inhibit gene transcription.
Antisense nucleic acid: Natural or synthetic oligonucleotides that are
complementary to the target mRNA that hybridize to, and inhibit translational
steps. |
| (*2) |
Phosphorothioate DNA:Stereocontrolled synthesis of phosphorus atom modified
nucleic acid derivatives.
Phosphorothioate DNA is a variant of natural DNA, in which one of the non-bridging
oxygens is replaced by sulfur. Development of stereocontrolled synthesis
of phosphorus atom modified (P-modified) nucleic acids is one of the main
themes of Chiralgen, Ltd. |
| (*3) |
What will be the results of achieving a practical implementation of asymmetrical
synthesis?
In general, physiological activities are different between stereoisomers
(the "right-" and "left-handed"). For example, the
(R) enantiomer of thalidomide is effective against morning sickness but
the (S) is teratogenic and causes birth defects (though the enantiomers
can interconvert in vivo). Therefore, establishment of stereocontrolled
synthesis of P-modified nucleic acids are strongly desired. |
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