All Submissions | J. Saba Submissions | Physics Site Links | Home Page |
| Email: James Saba |
GSJ: Received Apr. 18, 2007:
http://wbabin.net/saba/saba74.htm
Drug Discovery with Microarrays and Beads
James Saba
A prior report (1) teaches discovery of allosteric modulators of drug-resistant proteins. It has now been recognized a similar techniques can be used to find ligands which directly bind the wild-type target protein at the site normally occupied by a drug. Thus, providing direct leads to potential new drugs.
More generally the present invention teaches materials and methods for discovery of ligands (preferably small) which bind to a target macromolecule at a site normally occupied by a known ligand. In a preferred application of the invention, the ligand is a small organic drug.
The invention makes use of the tremendous parallel analytical capacity of microarrays and/or beads.
The target macromolecule (preferably comprising amino acids) may be an isolated, or may reside on a particle such as a cell.
Figure 1 delineates one preferred version of the invention wherein the members of a library of potential ligands to be screened are affixed to a microchip surface. While only 3 library members are shown, of course there are many more in practice.
Note that in this example the target protein is first bound to its drug, and that both are distinctly labeled, such as by a fluorescent dye or nuclear isotope.
Note also that while some library members bind the target molecule, we are primarily only interested in those which bind and displace the labeled drug. These are further analyzed to established direct binding of library member to that site bound by drug.
As previously described (1-3), beads could also be used as the support.
Optionally the surface of the support to which the library members are affixed can also have molecules or molecular features which generically bind to the target molecule at a site not bound to the know ligand, or to the particle to which the target molecule may be associated with (for example cell).
If it should be that the above invention is indeed novel any patentable rights I may have, I freely give away.
It is hoped that others will honor the invention as delineated above and by the following claims.
Claims
2) The process of claim 1 where the support is the surface of a biochip or microwell.
3) The process of claim 1 where the supports are beads or microspheres.
4) The process of claim 1 were said know ligand is labeled.
5) The process of claim 1 where the target molecule is labeled.
6) Claim 4 & 5.
1)
Allosteric Modulation of Drug Resistant Mutants
Saba, J Gen Sci J Apr.
15, 2007
2)
Discovery of Modulators of Polymerization.
Saba, J Gen Sci J Apr.
16, 2007
3)
Cell Surface Receptor Ligand Discovery.
Saba, J Gen Sci J Apr.
15, 2007
Figure 2 exemplifies the process using cells.
For a complete list of articles published by James Saba in the Gen Sci J, please go to http://www.wbabin.net/saba.htm