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Versatility of positional scanning synthetic combinatorial libraries for the identification of individual compounds
Author(s) -
Pinilla Clemencia,
Appel Jon R.,
Blondelle Sylvie E.,
Dooley Colette T.,
Eichler Jutta,
Ostresh John M.,
Houghten Richard A.
Publication year - 1994
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430330210
Subject(s) - acetylation , peptide , amino acid , peptide library , biochemistry , melittin , amino acid residue , peptide sequence , drug discovery , chemistry , trypsin , identification (biology) , combinatorial chemistry , biology , gene , enzyme , botany
Positional scanning synthetic combinatorial libraries (PS‐SCLs) offer a unique and rapid approach for the identification of individual active compounds from libraries made up of millions of compounds for basic research and drug discovery. As presented here, PS‐SCLs are free to interact in solution, and therefore can be screened in virtually any assay system to rapidly identify compounds. For example, a PS‐SCL made up of hexapeptides consists of six separate positional libraries, each composed of mixtures having a single position defined with an amino acid and the remaining positions as mixtures of amino acids. The screening of PS‐SCLs, in most instances, permits the identification of the most active amino acids at each position of a peptide in a single assay. To illustrate the versatility of this combinatorial library approach, three different hexapeptide PS‐SCLs are described: (1) N‐terminal acetylated, (2) N‐terminal non‐acetylated (both composed of L‐amino acids), and (3) N‐terminal acetylated composed of D‐amino acids. Each of the PS‐SCLs is composed of more than 50 million peptides; they are used here to identify: an antigenic determinant recognized by a monoclonal antibody; non‐acetylated peptide sequences that bind to δ opioid receptors; acetylated and non‐acetylated peptide inhibitors of melittin's hemolytic activity; and D‐amino acid peptide inhibitors of trypsin. © 1994 Wiley‐Less, Inc.