1. Overview

Most of the literature passages in this section were abstracted from Methods in Enzymology, Volume 276: Combinatorial Chemistry (Abelson, J. N., Ed.), Academic Press, San Diego, CA, 1996, which addresses molecular biological approaches to combinatorial selection strategies. More traditional chemical problems have also been solved using analogous approaches, as described in other articles from the volume that were not included here.

To illustrate the breadth of this emerging field, consider two recent Chemical and Engineering News articles. The first (Borman, 1999) describes problems that have both molecular biological and chemical aspects. The second (Dagani, 1999) describes chemical and materials science problems that have been solved using combinatorial approaches. These applications proceed via steps analogous to those used in the molecular biological selection scenarios. Comparing these analogies illustrates generalized features of all combinatorial programs and highlights key areas requiring improvement. This is necessary to fully appreciate the capabilities promised by such approaches in drug and materials discovery.

The following passages from the seminal article by Gold and colleagues (Irvine et al., 1991) describe the general steps in the Systematic EvoLution by Exponential (SELEX) enrichment method with RNAs targeted by RNA-binding proteins. Survivor RNAs are selectively bound in competitive reactions using sequence pools containing varying degrees of sequence randomization.

"After mixing a protein with a pool of RNA molecules in the appropriate buffer solution, protein-bound RNA molecules are separated from unbound RNA molecules by passing the solution through a nitrocellulose filter. Most protein sticks to the...