Mixture libraries

Wipf, P. Reeves, J.T. Balachandran, R. Ghiliano, K.A. Hamel, E. Day, B.W. (2000B) Synthesis and biological evaluation of a focused mixture library of analogues of the antimitotic marine natural product curacin A. J. Am. Chem. Soc., 122,9391-5. 

The structure determination of a library member by deconvolution can be used with either mixture libraries or those generated by split synthesis. Mixture libraries are formed by allowing a defined group of synthons to first couple to the support and then the process is repeated as described below until the library is complete. Because the chemistry... 

Fig. 1. Mixture library and deconvolution. (AAA) =all 20 amino acids simultaneously incorporated (AA) = one of 20 amino acids (AA) = preferred amino acid as determined by bioassay.

Fig. 2. Mixture libraries - position scanning. (AA) =one of 20 amino acids (AAA) = all 20 amino acids simultaneously incorporated.

Synthesis of mixture libraries and deconvolution of active sublibraries... 

Figure 3-1 Generic (a) and mixture (b) combinatorial libraries. The size of the generic library is the product of the various numbers of substituents (here, 2x2x4 X 5. or 80). The size of the mixture library IS simply the total number of structures.

Ubrary A collection of structures, cither a generic library (baiicd on some icalTold plus multiple residues) or a mixture library (containing diverse. scaffolds). The number of. specific structures in a library is either the product of the numbers of residues pos.sible at each variable position (for a generic library) or. simply the sum of the number of structures (for a mixture library). 

The synthetic advantages of preparing mixtures instead of individual compounds are offset by the need to deconvolute mixture libraries following bioassay. Deconvolution shortcuts, such as synthesis of multiple libraries containing orthogonal pools (36), are sometimes useful but can only be relied on when the activity of the mixture results from a single highly active compound. Keep-... 

CWS symbol for gasoline thickened with latex, used as a filler for incendiary bombs Landing craft, infantry Landing craft, mechanized Landing craft, vehicle and personnel Lewisite-mustard mixtures Library Letter... 

As shown by these exan les, the use of small focused mixture libraries was found to be a highly effective parallel synthesis approach by providing new, potent enzyme inhibitors while eliminating over 73% of the synthesis and testing effort that would have been required if each confound was prepared and tested individually. 

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