All D-amino acid hexapeptide inhibitors of melittin's cytolytic activity derived from synthetic combinatorial libraries.
The identification of peptides that inhibit the biological functions of proteins was used as a means to explore protein/ligand interactions involved in molecular recognition processes. This approach is based on the use of synthetic combinatorial libraries (SCLs) for the rapid identification of individual peptides that block the interaction of proteins with their biological targets. Thus, each peptide mixture of an all-D-amino acid hexapeptide SCL in a positional scanning format was screened for its ability to inhibit the hemolytic activity of melittin, a model self-assembling protein. The potent inhibitory activity of the identified individual peptides suggests that protein-like complexes are able to specifically bind to peptides having an all-D configuration. These results also show that SCLs are useful for the identification of short, non-hydrolysable sequences having potential intracellular inhibitory activities.
Blondelle
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Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
Houghten
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Pérez-Payá
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D000595:Amino Acid Sequence; D001665:Binding Sites; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D008555:Melitten / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D010455:Peptides; D008555:Melitten