Positional scanning deconvolution method

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... 

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. 

These techniques can be broadly split into two groups, the first of which can be represented by pooling methods, where deconvolution is obtained via various chemical steps, run in parallel or after the library synthesis. Pooling methods normally require multiple synthesis of many library members, including inactive individuals, in different pool formats. They are not single bead methods, so they are independent from analytical methods for structure determination. This group includes iterative deconvolution, recursive deconvolution, subtractive deconvolution, positional scanning and mutational... 

Iterative deconvolution Recursive deconvolution Subtractive deconvolution Positional scanning/indexing Mutational surf other methods... 

Boger et al. [47] introduced the so-called deletion synthesis deconvolution as a process typical for convergent dimerization libraries, based on the methodical elimination of one element from the variable library units and on the evaluation of loss vs. gain of activity. This method was compared with positional scanning in a following paper by the same group [48] and proved to be effective and useful. 

A process called deconvolution is commonly employed to determine biological activity.The final library pools are not combined but are tested as either on-bead or detached compound mixtures. The most active pool defines which synthon is preferred in the last step. The synthesis is repeated to the penultimate set of pools and these are then allowed to react with the best last step synthon. Alternatively, pools of conserved resin from the penultimate step held back during the original synthesis may be used. The most active pool found on retesting defines the best last two synthons. This process is repeated until the most active member is identified. A somewhat similar method termed position scanning also has found successful application, especially in the analysis of peptides. ... 

ITERATIVE DECONVOLUTION RECURSIVE DECONVOLUTION SUBTRACTIVE DECONVOLUTION POSITIONAL SCANNING/INDEXING MUTATIONAL SURF OTHER METHODS... 

Figure 1 Schematic representation of the positional scanning method of deconvolution.

Positional scanning, a non-interative method for peptide library deconvolution. Positional scanning relies on the synthesis of partial compound libraries that represent first-order sub-libraries in which one position of the peptide sequence is kept invariant while aU other positions are varied. Once biological activity has been detected in the complete library, aU the sub-libraries are screened additionally in the same biological assay. Consequently, positional scatming reveals the optimum residue for every position in a peptide. 

There are several ways to deconvolute or identify the individual active compounds in an active mixture. These include iterative resynthesis and the synthesis of overlapping mixtures, such as the positional scanning method of Houghten et al." In iterative resynthesis, the most active pools are resynthesized as several smaller subpools with a variable position resolved. This process is repeated until every position has been resolved and individual active compounds have been made. In Houghten s method, the complete library is... 

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