Application of one-read one-structure approach to identification of nonpeptidic ligands

A synthetic chemical library comprised of alkylated and acylated amino acids was synthesized and screened to determine structures that bind to a model target, streptavidin. The library was prepared using 'split synthesis' and screened in a solid phase binding assay. The structure of positively reacting compounds was determined using mass spectroscopy. Positive compounds, together with various structural analogs were synthesized and their binding confirmed. Structures containing both an imidazole moiety and a substituted aromatic residue demonstrated binding.