Combinatorial chemistry molecular evolution

Klekota, B. Miller, B. L. Selection of DNA-binding compounds via multistage molecular evolution. Tetrahedron 1999, 55, 11687 (Combinatorial Chemistry Symposium in Print). 

A significant number of reviews and books on combinatorial libraries [1 1], molecular diversity [5-8], and solid-phase synthesis [9,10] have appeared in the last 3 years. For a more in-depth look at the evolution of this area, the reader is referred to these publications. In addition, a new journal has been started dealing with molecular diversity. This journal, Molecular Diversity, is published by ESCOM and is available in printed and electronic form. Associated with it is an Internet worldwide web site devoted to combinatorial chemistry and molecular diversity which can be accessed as www.vesta.pd.com. 

Herrmann A (2009) Dynamic mixtures and combinatorial libraries imines as probes for molecular evolution at the interface between chemistry and biology. Org Biomol Chem 7 3195-3204... 

What we are doing is related, in a way, to both biological evolution and the principles of combinatorial chemistry. Our work aims at narrowing down the diversity of possible answers to the question of why Nature chose the specific structure of DNA (actually RNA) and not some alternative type of molecular structure as a genetic system. 

Levitan, B. Models and search strategies for applied molecular evolution In Annual Reports in Combinatorial Chemistry and Molecular Diversity, Moos, W. H., Pavia, M. R., Kay, B. K., Ellington, A. D., Eds. Escom Leiden, 1997 Vol. 1, p 95-152. 

In the context of combinatorial chemistry, as well as in natural products chemistry, it is quite possible that the analyte of interest is not contained in spectrum databases. In recent years, the use of structural (or compound) databases for structure elucidation has increased due to the evolution of web-based services such as PubChem [218] and ChemSpider [259], with approximately 26 million entries each. These databases do not generally contain spectra (there are some exceptions) and as such only provide information about compounds that have been documented to exist. Although this is a smaller subset of possible structures for a given molecular formula than generating all mathematically possible structures, the same principles apply to determining the correct one as for generated structrues, without the guarantee that the correct struc-... 

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. 

---