GSJ: Received Apr. 15, 2007: http://wbabin.net/saba/saba70.htm

Drug resistance is a serious problem in medicine. Indeed it was astonishing to recently read that Gonorrhea (one of the most prevalent sexually transmitted diseases) is rapidly becoming drug resistant (1).

The present invention involves means for discovery of molecules (preferably small) which allosterically alter the binding of a protein to a second molecule. A prime objective is to discover allosteric modulators of drug resistant proteins such that they are again susceptible to the drug. The invention also provides a means of finding allosteric modulators of wild-type protein which induce the wild-type protein to bind (and perhaps be inhibited by) a molecule which it does not normally bind.

Figure 1 delineates one preferred embodiment of the invention.

Various means of encoding beads (including microspheres) are well known, as are methods of synthesizing libraries of compounds on such beads. Alternatively to encoding the bead, a library member could be directly identified such as by mass spectrometry.

The molecular library attached to such beads could be of any class, such as small organics, peptides, or oligonucleotides.

Labeling of the drug used in the mixture of the target protein can be of various means, including fluorescence and the use of nuclear isotopes.

The target protein may be isolated, or residing on the surface of a particle such as a cell.

If fluorescence is used a flourescence-activated cell sorter, or a fiber-optic picotiter plate (2,3,4) could be used to isolate those beads which have effected a complex of bead-protein-drug.

If radioactivity is used, the beads could be made of scintillating material and those beads which have bound drug and scintillate could be identified. Preferably this is done using a fiber-optic picotiter plate.

Once the appropriate library members are isolated, they are identified by decoding the beads.

Finally the library members can be individually tested for function.

Notice that this process could also be used to find allosteric modulators which displace a target-bound labeled molecule.

As an alternative to the above process, it is conceivable that the unlabeled drug could be affixed to the beads, and these could be combined with a mixture of the target protein and a library of soluble labeled molecules.

Lastly, notice a similar simpler process could be used to isolate library members which simply bind a protein. Therein only a labeled protein would be combined with the bead library. Labeling could be prior or subsequent to bead binding.

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

References

1) CDC Shifts Gonorrhea Treatment Advice

2) Pyrosequencing using fiber-optic picotiter plates.

3) Sequencing by synthesis based ordered restriction mapping.
Fuerst, et al US Patent Appl 20070082358 April 12, 2007

4) Nucleic acid sequencing using microsphere arrays.
Chee, et al US Patent Appl 20050191698, September 1, 2005

Addendum April 16, 2007:

Besides using an array of beads, it would also be possible to use a planar chip array, such as that resulting from lithographic production of a library of peptides or polynucleotides.

Claim 1) A process of identifying a allosteric modulator of a target protein's binding of a labeled molecule, which comprises contacting an array of different molecules with a target protein, and a labeled molecule.

Claim 2) The process of claim 1 where a trimer complex of a arrayed library molecule+target protein+labeled molecule is formed and detected.

Claim 3) The process of claim 1 or 2 wherein the array is fabricated photolithographically.

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For a complete list of articles published by James Saba in the Gen Sci J, please go to http://www.wbabin.net/saba.htm