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.
Dooley
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Torrey Pines Institute for Molecular Studies, San Diego, CA 92121.
Houghten
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D000595:Amino Acid Sequence; D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D016208:Databases, Factual; D007256:Information Systems; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000700:Analgesics; D010455:Peptides; D011957:Receptors, Opioid