Immtech issued gene expression control patent
used to control gene expression, which will add to the potential
use of Immtech's compounds as small molecule drugs that can control
gene expression selectively.
In addition, this patent is set to provide treatments for microbial infections, cancers and disorders of genetic origin or uncontrolled cell proliferation.
Stacked dimers represent a powerful new motif for specific, strong recognition of mixed base pair DNA sequences. Heterocyclic dimer systems provide significant new understanding of the molecular basis of DNA recognition and how it is affected by the local interplay of base pair chemistry, solvent and ligand properties. The clinically useful and cell permeable hetercyclic motif is unique in targeting mixed sequences of DNA.
Design and discovery of molecules that can regulate gene expression in cells in a desirable and predictable manner is a central goal of research at the interface of chemistry and biology. The developing field of "chemical genetics" requires molecules that have the necessary selectivity to recognise target genes.
Immtech Consortium scientists initially discovered that certain unfused aromatic cationic molecules can specifically recognise and bind to not only narrow, DNA minor groove pockets rich in adenosine-thymine (or "AT") nucleic acid sequences, but also to wider minor groove pockets formed by sequences rich in guanosine-cytosine (or "GC") nucleic acid bases.
The latter binding requires the drug molecules to stack on top of one another as a "stacked dimer" to fit into the wider spaces defined by these base pairs. When drug molecules bind to any of these DNA sequences, they may be able to control the expression of certain genes and regulate biochemical processes critical to cell function.
In cancer, there is heightened focus on the ends of chromosomes called telomeres. Telomeres are rich in polymeric sequences of guanosine bases that normally shorten each time a cell divides.
An enzyme called telomerase, found in approximately 90 per cent of cancer cells and selected normal tissues, prevents the shortening of the poly G sequence, resulting in an immortalized cell that continues to divide and may form a tumour. By specifically binding to sequences rich in guanosine bases, stacked aromatic cations may be able to block the activity of telomerase and produce an important anti-cancer effect.
Dr Lawrence Potempa, Immtech's chief science officer and vice president of research stated: "This discovery by Dr Wilson and his colleagues has profound implications in the development of new strategies and drug substances that may be able to target specific diseases at the genetic level."
"The unique nature of this class of compounds gives Immtech a position in developing drugs to control and regulate cell proliferation and gene expression," he added.
The patent (6,867,227), is entitled "Compounds that Exhibit Specific Molecular Recognition of Mixed Nucleic Acid Sequences and Bind the DNA Minor Groove as a Dimer.
