THE USE OF POSITIONAL SCANNING SYNTHETIC PEPTIDE COMBINATORIAL LIBRARIES FOR THE RAPID-DETERMINATION OF OPIOID RECEPTOR LIGANDS

The application of a new synthetic peptide combinatorial library (SPCL) is described. This library, termed a positional scanning SPCL, contains six positional SPCLs, each of which contains all possible hexameric combinations of 18 of the 20 natural L-amino acids (18(6) = 34,012,224 peptides). Each positional SPCL (O1XXXXX-NH2, XO2XXXX-NH2, XXO3XXX-NH2, XXXO4XX-NH2, XXXXO5X-NH2, and XXXXXO6-NH2) was used to determine the most active amino acid for the six positions of a hexamer. Combinations of these amino acids were used to synthesize 24 individual peptides, which were then tested for activity. The most active peptide found corresponded to a hexameric analogue of methionine-enkephalin. Results obtained in this study are compared to those obtained using the SPCL described earlier (1) (O1O2XXXX-NH2), and the subsequent iterative process.