Newer deconvolution methods and expansions of library diversity

Newer deconvolution methods and expansions of library diversity 

The original iterative method for deconvolution remains robust and highly useful. However, there are opinions that the resynthesis aspect makes this deconvolution slow to yield individual hits, although no study is known that comparatively quantifies this. In order to overcome this perception, a number of research groups are actively developing additional deconvolution methods for mixture-based libraries. 

A rather powerful deconvolution method reported is positional scan deconvolution developed by Houghten and co-workers [56] (Fig. 4). In this method a number of copies 

For heterocychc libraries in a positional scan format, a key factor is in being able to devise a method for efficiendy carrying out the construction of the library in the positional scan format. For peptide hbraries, the Houghten laboratory was able to employ mixtures of building blocks where the molar ratios had been adjusted to account for reactivity (kinetic rate) differences of incoming building blocks and thereby achieve equimolar mixtures. A non-peptide, two-dimensional positional scan library, identified as an indexed combinatorial library, was reported recently [63], In this work a novel acetyl- 

Although not identical, both the orthogonal and positional scan formatted libraries share the features that all mixtures are made at the start of the library process and only individual compound synthesis is required after the first screening of mixtures. This is an extra initial effort with regard to the synthesis of mixtures when compared to an iterative method. The advantage is that no intermediate mixture syntheses will be required. If prepared in sufficient quantity, the library can be screened over a large number of assays, and the added effort of initial mixture syntheses will be translated into an efficiency in deconvolution relative to the continual resynthesis of mixtures with iterative deconvolution. 

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