Optimization of the synthesis of peptide combinatorial libraries using a one-pot method.

Conditions for the synthesis of synthetic peptide combinatorial libraries (SPCLs) from mixtures of amino acids were explored. In a one-pot synthesis, the effect of the starting concentrations of amino acids on the resulting library composition was studied, and the optimum balance of amino acids was determined. Protein sequencing, MALDI-TOF, and amino acid analysis were used for the evaluation of the libraries, and their relative merits-are discussed. The effects of continuous-flow automated synthesis instrumentation in conjunction with polyethylene glycol-polystyrene (PEG-PS) graft supports and various cleavage cocktails on the successful synthesis of SPCLs were examined.