Combinatorial receptor finding - large and random vs. small and focused libraries

Whereas in the classical combinatorial approach mainly large but completely random libraries are used, nowadays also the use of small but designed libraries is coming into focus. We discuss the pros and cons of these two different approaches, using examples from literature work and our own studies showing how combinatorial libraries are applied in supramolecular chemistry e. g. to identify artificial receptors for peptide binding in aqueous solvent.