Combinatorial peptide synthesis: statistical evaluation of peptide distribution.

Peptide libraries are large collections of oligopeptides used as screening mixtures for the discovery of new pharmacological leads. Their synthesis is achieved on solid phase in a combinatorial way, one of the reacting components being either a mixture of resin-bound amino acids or peptides, or a mixture of amino acids in solution. In practice, the various peptides are not represented in equimolar amounts in the resulting libraries. Here, Jean Boutin and Alban Fauchère explain the statistical considerations important in the design of a peptide library, show to what extent one bead-one peptide libraries fulfill statistical criteria, and discuss resin bead quantities necessary to minimize the range of relative concentrations of the different peptides present in the library. This range is crucial in the correct interpretation of the results of biological tests.