Combinatorial chemistry, overview

WA WaiT. Combinatorial chemistry and molecular diversity. An overview. J Chem Inf Comput Sci 37 134-140, 1997. 

Chisholm B, Potyrailo R, Cawse J, Shaffer R, Brennan M, Molaison C, Whisenhunt D, Elanagan B, Olson D, Akhave J, Saunders D, Mehrabi A, Eicon M (2002) The development of combinatorial chemistry methods for coating development -1. Overview of the experimental factory. Prog Org Coat 45 313-321... 

Schmid, D. G., Grosche, P., Bandel, H., and Jung, G. (2000). FTICR-mass spectrometry for high-resolution analysis in combinatorial chemistry. Biotechnol. Bioeng. 71 149-161. Scigelova, M., and Makarov, A. (2006). Orbitrap mass analyzer—Overview and applications in proteomics. Proteomics 6 (Suppl. 2) 16-21. 

This chapter is intended to provide an overview of the field of mixture-based combinatorial chemistry. It deals with reports of library preparation and utilization for the period from the beginning of 1995 to mid-1996. As this is the first Report in this planned series, some discussion of pre-1995 work will be included to set the proper context for the more recent work. The discussion will cover the methods of preparation of mixture-based libraries, the means of identifying actives from the mixtures, and the rationale for using mixtures. 

Most of the mass spectrometry applications for combinatorial chemistry will be described in the following sections of this chapter. Here we will give a short overview of MS techniques utilized for the characterization of resin-bound molecules. The majority of publications in this field describe applications of matrix-assisted laser desorption ionization (MALDI), combined with time-of-flight (TOF) detection. The major difference of MS application for analysis of resin-bound molecules from the above-described NMR and IR applications is that analyte should not be covalently bound to solid support prior to mass measurement. Detachment of compound molecules from resin can be done chemically (for example, by bead exposure to TFA vapors) [30,31] or photochemically, such that cleavage, desorption, and ionization of molecules occur simultaneously upon stimulation by laser radiation [32], Since the... 

A short overview of synthetic strategies that are currently used in combinatorial chemistry is important to get a better understanding of how to characterize a combinatorial library in the most efficient way. Figure 10.3 presents different strategies for synthesis of combinatorial libraries on an example of a library with three points of randomization (X, Y, Z), three building blocks in each randomization (XI, X2, X3, Yl, Y2, etc., correspondingly), and total complexity of 27 compounds. 

III. BRIEF HISTORICAL OVERVIEW OF THE BUSINESS DEVELOPMENT OF COMBINATORIAL CHEMISTRY... 

Valuable to technologists and researchers as an introductory survey on the many aspects of combinatorial chemistry and combinatorial technology, this book offers an overview of a field that promises broad applicability in the identification of new drugs, as well as in diagnostics, new materials, and catalysis. 

For an overview of the information management issues associated with combinatorial chemistry, see SM Muskal. Information management. In AW Czarnik, SH DeWitt, eds. A Practical Guide to Combinatorial Chemistry. Washington, DC ACS Books, 1997, pp 357-397. 

In the following, an overview of equipment that is currently available commercially is presented. Especially in the early days of combinatorial chemistry, when little was available commercially, a significant number of companies designed and built their own robotic equipment. These proprietary solutions, as well as peptide synthesizers, are not listed herein. 

Ring formation is a very important reaction in synthetic chemistry. This is particularly true for heterocyclic structures since they play a central role in medicinal chemistry, a field where combinatorial chemistry nowadays finds its most important application. Table 3.10 provides an overview over the achievements that have been made in combinatorial synthesis of carbo- and heterocyclic rings. 

This chapter aims to present an overview on the main peptide bond modifications which have been proposed in the recent years. The solution- and solid-phase synthesis of the new synthetic oligomers, the methods for their characterization, and their biological and folding properties will be discussed. Particular emphasis will be given to those modifications which are suitable for combinatorial chemistry applications and developments. 

After a short overview of existing methods, we will highlight in this chapter on several practical aspects of HR MAS NMR. We will underline the efficiency of HR MAS NMR studies by introducing experiments to quantitatively monitor solid-phase supported reactions and describing a method that allows the use of protonated solvent. Recently published reviews covering NMR methods, analytical tools in combinatorial chemistry and in the drug discovery process may be used to have an easy access to this exciting field [2-4]. 

Combinatorial Chemistry begins with a general overview on recent advances in the subject, with expert surveys provided on selected solid-phase organic reactions and - for the first time - also on solution-phase combinatorial chemistry. These chapters are followed by a detailed survey of the broad research into multicomponent reactions. 

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