The use of positional scanning synthetic peptide combinatorial libraries for the rapid determination of opioid receptor ligands

Abstract

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 (O 1XXXXX-NH 2, XO 2XXXX-NH 2, XXO 3XXX-NH 2, XXXO 4XX-NH 2, XXXXO 5X-NH 2, and XXXXXO 6-NH 2) 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) (O 1O 2XXXX-NH 2), and the subsequent iterative process.