Genetically-encoded combinatorial peptide libraries are convenient tools to identify
peptides to be used as therapeutics, antimicrobials and functional synthetic biology
modules. Here, we report the identification and characterization of a cyclic peptide,
G4CP2, that interferes with the GAL4 protein, a transcription factor responsible for
the activation of galactose catabolism in yeast and widely exploited in molecular
biology. G4CP2 was identified by screening CYCLIC, a Yeast Two-Hybrid-based
combinatorial library of cyclic peptides developed in our laboratory.
G4CP2 interferes with GAL4-mediated activation of galactose metabolic enzymes
both when expressed intracellularly, as a recombinant peptide, and when provided
exogenously, as a chemically-synthesized cyclic peptide. Our results support the
application of G4CP2 in microbial biotechnology and, additionally, demonstrate that
CYCLIC can be used as a tool for the rapid identification of peptides, virtually without
any limitations with respect to the target protein. The possible biotechnological
applications of cyclic peptides are also discussed.
