Library analysis overview

Here, we present an overview of the aspects of the design, synthesis, analysis, and screening of combinatorial solid-phase glycopeptide libraries as compared to parallel glycopeptide arrays. 

From the FIA—MS overview spectrum, speculation that there can be more than just one structurally defined molecule type behind an observable signal i.e. the presence of isobaric compounds, cannot be excluded whenever one signal defined by the m/z-ratio is examined in FIA-MS spectra. Consequently, the information obtained by FIA-MS is quite limited whenever we deal with complex mixtures of environmental pollutants rather than the analysis of pure products or formulations with a known range of ingredients. LC separation is inevitable when mixtures of isomeric compounds should be identified with MS-MS. Therefore, in FIA-MS-MS special attention has to be paid to avoid the generation of mixed product ion spectra from isomeric parent compounds. This would block identification by library search and may lead to misinterpretations of product ion spectra because of the fragmentation behaviour observed. 

The concepts of molecular similarity (1-3) and molecular diversity (4,5) play important roles in modern approaches to computer-aided molecular design. Molecular similarity provides the simplest, and most widely used, method for virtual screening and underlies the use of clustering methods on chemical databases. Molecular diversity analysis provides a range of tools for exploring the extent to which a set of molecules spans structural space, and underlies many approaches to compound selection and to the design of combinatorial libraries. Many different similarity and diversity methods have been described in the literature, and new methods continue to appear. This raises the question of how one can compare different methods, so as to identify the most appropriate method(s) for some particular application this chapter provides an overview of the ways in which this can be carried out, illustrating such comparisons by,... 

This previous review provides a comprehensive overview of the major chromatographic methods for the analysis of tocopherols and tocotrie-nols developed until about 2000. The current chapter is not a comprehensive overview, but instead is a summary of the major advances in the field that have occurred since 2000. Two other valuable resources that review methods for the analysis of tocopherols and tocotrienols are the websites AOCS Lipid Library (2011) and Cyberlipid (2011). 

Essentially, the similarity between componnds is estimated in terms of a distance measnre between two different objects, described by vectors. Scaling of the variables is advisable if they do not have comparable magnitnde. The most prominent distance measnres are the Enclidean distance, the average Enclidian distance, and the Manhattan distance. A comprehensive overview of methods for chemical similarity searching has been pnblished by Willet et alP Except for similarity searches among componnds in databases, snch similarity measnres are freqnently applied in the design and analysis of combinatorial libraries." ... 

Both qualitative and quantitative information can be derived from multivariate analysis. A qualitative classification model provides overviews of how the properties relate to each other and how changes can be made to molecules in a qualitative sense. The main goal for qualitative analysis is to assist understanding and put all the pieces of the puzzle together. A quantitative model focuses on accurate prediction of various desirable properties for designing new molecules and combinatorial libraries with good potency and druglike properties. 

In this chapter, we will start by providing an overview of the evolution of the 3D pharmacophore concept and subsequently show the usefulness of 3D pharmacophore searching in modern lead discovery. The use of this approach for combinatorial library design, compound classification, and molecular diversity analysis is presented. Examples of successful applications reported in the last couple of years are reviewed. 

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