SCREENING USING BIOLOGICAL TARGET MOLECULES WITH METAL-ION BINDING SITES

摘要

The present invention provides a molecular approach for rapidly and selectively identifying small organic molecule ligands, i.e. compounds, that are capable of interacting with and binding to specific sites on biological target molecules. The methods of the present invention are applicable to any biological target molecule that has or can be manipulated to have a metal ion binding site. A very interesting group of molecules are membrane proteins such as 7TM transmembrane proteins. The methods described herein make it possible to construct and screen libraries of compounds specifically directed against predetermined epitopes on the biological target molecules. The compounds are initially constructed to be bi-functional, i.e. having both a metal ion binding moiety enabling them to bind to a natural or artificial metal ion binding site, and a variable moiety, which is varied chemically to probe for interactions with specific parts of the biological target adjacent to the metal ion binding site. Compounds may subsequently be further modified to bind to the unmodified biological target molecule without help of the bridging metal ion.