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

• Published in: Life sciences (1973) Vol. 52; no. 18; pp. 1509 - 1517
• Main Authors: Dooley, Colette T., Houghten, Richard A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 1993; Elsevier
• Subjects: Amino Acid Sequence; Analgesics - chemical synthesis; Analgesics - pharmacology; Animals; Biological and medical sciences; Cell receptors; Cell structures and functions; Databases, Factual; Fundamental and applied biological sciences. Psychology; Information Systems; Molecular and cellular biology; Molecular Sequence Data; Neuropeptide receptors; Peptides - chemical synthesis; Peptides - metabolism; Peptides - pharmacology; Radioligand Assay; Rats; Receptors, Opioid - drug effects; Receptors, Opioid - metabolism; Structure-Activity Relationship; Opiate receptor; Molecular position; Combinatorial method; Synthetic product; Peptides; Structure activity relation; Databank; Ligand; Biological activity; Hexapeptide
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/0024-3205(93)90113-H

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.