Combinatorial techniques applicable

The application of evolutionary and combinatorial techniques to study and solve complex biological and chemical problems has become one of the most dynamic fields in chemistry and biology. The book presented here is a loose collection of articles aiming to provide an overview of the current state of the art of the directed evolution of proteins as well as highlighting the challenges and possibilities in the field that lie ahead. 

On one side, application of combinatorial chemistry to sensor discovery could be traced back to very early time, as the receptor discovery has been recognized as an important applicable field for combinatorial chemistry as in medicinal chemistry.15 In this approach, combinatorial techniques are utilized to compensate receptor design, and the fluorophore can be either incorporated into the receptor synthesis or remain independent for displacement assays. Diversity of the receptor part helps for probing the interactions between the receptor and target analyte, thus this approach can greatly facilitate the target-oriented approach in the situations that the receptor is unknown or not easily designed.16 One recent example of mercury sensor development clearly demonstrated the power of this approach (Fig. 17.4).17... 

Various types of PSRs are described in the following sections. However, rather than classify these reagents by the type of support or by functionality, a classification based on the method of preparation is used here, with the focus on the most commonly employed techniques. Furthermore, rather than providing an exhaustive list of all PSRs described in the literature, the aim of this chapter is to provide an understanding of the principles of preparation and application of such reagents, with a special focus on important reactions and on the combination of several PSRs in one synthetic sequence or, where possible, in one pot. The latter is a rather novel and highly interesting aspect of combinatorial chemistry applications. 

From the experimental studies presented here, we conclude that it is possible to introduce the combinatorial technique in the Langmuir monolayer research. The application of lipid libraries instead of the traditional one or a few lipids for monolayer formation provides a unique approach to generating artificial proteins or other molecular receptors. The supramolecular species with proteinlike structures located on the surface of the monolayer can be readily used for biomimetic sensor development after the deposition of the film on a transducer such as an optic fiber. This combinatorial surface chemistry research may become a very important research area in Langmuir and Langmuir-Blodgett film smdies. 

One of the most important applications of anionic polymerization is to prepare a block copolymer. It may be pointed out that all monomers do not respond to this technique, which means that only limited block copolymers can, in reality, be synthesized. During the present time, as pointed out in Chapter 1, there is considerable importance placed on finding newer drugs. Therein, we also described combinatorial technique in which we showed the importance of solid supports on which chemical reactions were carried out. However, these reactions can occur provided reacting fluids can penetrate the solid support in other words, it should be compatible with the sohd supports. 

The basic scheme of this algorithm is similar to cell-to-cell mapping techniques [14] but differs substantially In one important aspect If applied to larger problems, a direct cell-to-cell approach quickly leads to tremendous computational effort. Only a proper exploitation of the multi-level structure of the subdivision algorithm (also for the eigenvalue problem) may allow for application to molecules of real chemical interest. But even this more sophisticated approach suffers from combinatorial explosion already for moderate size molecules. In a next stage of development [19] this restriction will be circumvented using certain hybrid Monte-Carlo methods. 

The major impetus for the development of solid phase synthesis centers around applications in combinatorial chemistry. The notion that new drug leads and catalysts can be discovered in a high tiuoughput fashion has been demonstrated many times over as is evidenced from the number of publications that have arisen (see references at the end of this chapter). A number of )proaches to combinatorial chemistry exist. These include the split-mix method, serial techniques and parallel methods to generate libraries of compounds. The advances in combinatorial chemistry are also accompani by sophisticated methods in deconvolution and identification of compounds from libraries. In a number of cases, innovative hardware and software has been developed tor these purposes. 

In addition, further automation will be needed in what is still very much a hands-on art. Autoinjectors coupled to complete analytical data systems and readers for 96-well plates are the beginning of what will continue to be a necessary trend of residue chemistry. The application of the techniques of combinatorial chemistry/biochemistry, which has produced screening methodology for handling many variables, might be appropriate to residue chemistry. 

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