Chemistry, kinds combinatorial

Codon (mRNA), 1109-1110 table of, 1110 Coenzyme, 162, 1042 table of, 1044-1045 Coenzyme A, structure of, 817, 1044 Coenzyme Q, 632 Cofactor (enzyme), 1042 Color, perception of, 503-504 UV spectroscopy and. 503-505 Combinatorial chemistry, 586-587 kinds of, 586... 

At first, combinatorial chemistry focused on peptide and nucleotide libraries synthesis, but because poor pharmacokinetical properties cause poor oral availability of this kind of molecule, there is increasing interest in the development of new methods to prepare small, drug-tike molecules which obey lipinski s mle of five [303]. Heterocyclic compounds can offer a high degree of structural diversity and have proven to be useful as therapeutic agents. For these, there are recent advances in the preparation of heterocycles on solid supports [304]. The examples reported in this section are organized by their ring size. 

Most important of all, however, is the possibility of running the Merrifield procedure on any number of resin beads (or other support systems) simultaneously in a number of reaction chambers. An example of this alternative is the so-called split and mix system of combinatorial chemistry. The first step in this kind of system is to prepare some number of monomer-support units (three in the example shown below), in which the monomer present differs from chamber to chamber. In the diagram below, the units are represented as -X, -Y, and -Z. These three units are washed and then mixed with each other in a single container. The mixture is then divided and placed into three separate containers. One of the most common containers used contains a number of wells in a plastic or glass dish that are miniature versions of the common petri dish used in biology experiments. 

Combinatorial chemistry can produce many different products and also many different kinds of products. For example, it can produce peptide drug leads against multiple disease targets, or drug leads based on entirely different molecular scaffolds against multiple diseases, or even high-affinity ligands for purification purposes, in addition to products that are used to make and screen libraries. Combinatorial chemistry thus produces a vast array of different products. 

Combinatorial chemistry can produce many different products and also many different kinds of products. For example, it can produce peptide... 

The early days of solid-phase chemistry were mainly dedicated to the field of peptide synthesis. Peptide chemists have now fully incorporated these techniques in the way they carry out chemistry and very few of them nowadays would prepare a tetrapeptide in solution on a laboratory scale. As combinatorial chemistry has turned to the development of smaller libraries of low molecular weight compounds, almost all kinds of reactions can be carried out... 

A site worth watching for the future is http //www. combichemlab.com. This academic-oriented site is intended to provide free on-line information in the areas of combinatorial chemistry, high-throughput screening, and other related topics. Refreshingly, fhese days, there are no specials, offers or advertisements of any kind. 

Combinatorial chemistry can perhaps help discover new catalyst formulations for reactions presently of particular interest, such as oxidations or ammoxidation, and generally all reactions of alkanes. Reactions traditionally made in different kinds of processes are frequently shown to be also activated by heterogeneous catalysts (e.g., epoxidations). Reactors of unexpected design allow surprisingly selective reactions (e.g., monoliths for the oxidative dehydrogenation of light alkanes). However, the distance often remains long between these discoveries and the manufacture of active and selective catalysts adequately structured for particular use in an industrial reactor inserted in an industrial plant. 

This kind of chemistry is also considered a form of rational design because it is an attempt to eliminate the serendipity of conventional screening methods thanks to the application of the rules of combinatorial mathematics and algorithms of selection. Nevertheless, for a number of chemists combinatorial chemistry is a contemptible method of fabricating substances, and Pierre Laszlo has even talked of the moronic travesty of scientific research known as combinatorial chemistry . For Laszlo, it is a perversion of scientific chemistry pitifully limited to one single goal, the proliferation of chemicals . 

When, as a synthetic chemist, you look at the structure of RNA, you may ask yourself how did this particular type of molecular structure enter the scene for the first time If you adhere to the principles of evolution, you are led to conclude that the structure is the result of a selection process. Selection from what An important possibility is that RNA had been selected (or had selected itself) from a combinatorially formed library of alternative structures. Again, if you, as a synthetic chemist, hypothesize about the type of chemistry that could have produced RNA for the first time, chemical reasoning leads you to consider that there are many chemically closely related alternative structures that could have had a comparable chance to be formed by the same kind of chemistry. In such a scenario, RNA was selected, or had selected itself, by functional criteria from a library of structurally related nucleic acid alternatives. Such a view defines a strategy for approaching the question experimentally you systematically make such potentially natural alternatives in the laboratory by chemical synthesis and compare them with RNA with respect to those chemical properties that are known today to be relevant for RNA s biological functions. Such comparisons may tell you. 

---