Pharmacophore recombination for the identification of small molecule drug lead compounds

A method for screening a library of small organic molecules for one or more candidate target binding fragments (CTBF's) that bind to a target biological molecule (TBM), each CTBF having a linkable functional group (LFG) or blocked form thereof (BLFG), wherein the LFG or BLFG contains a disulfide linking group (LG), the method comprising:

• (a) contacting the TBM with individual members of a library of the CTBF;
• (b) detecting or determining which CTBF's bind to the TBM;
• and
• (c) selecting CTBF's that bind to the TBM;
• wherein the library is represented by the formula:
• CTBF-S-S-R8
• wherein R8 is
• a straight chain or branched alkyl of 1 to 10 carbon atoms that is optionally substituted with up to five groups selected from the group consisting of halide, alkyl, aryl, heteroaryl, carboxy ester, carboxamide, amino, n-acylamino, alkoxy, hydroxy, mercapto, phosphono and sulphono;
• or
• an aryl or heteroaryl that is optionally substituted with halide, alkyl, aryl, halide, heteroaryl, carboxy ester, carboxamide, amino, n-acylamino, alkoxy, hydroxy, mercapto or phosphono;
• and wherein each CTBF of the library further comprises at least a second LG selected from the group consisting of amide, secondary amine, ureido, thiourea, carbamate and sulfonamide.