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, able to interfere with the GAL4 protein, a transcription factor responsible for the activation of galactose catabolism in yeast and widely exploited in molecular biology. G4CP2 has been 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 limitation with respect to the target protein. The possible biotechnological applications of cyclic peptides are also discussed.

The cyclic peptide G4CP2 enables the modulation of galactose metabolism in yeast by interfering with GAL4 transcriptional activity / S. Rosa, A. Tagliani, C. Bertaso, L. Tadini, C. Visentin, L.J. Gourlay, S. Pricl, L. Feni, S. Pellegrino, P. Pesaresi, S. Masiero. - In: FRONTIERS IN MOLECULAR BIOSCIENCES. - ISSN 2296-889X. - 10:(2023), pp. 1017757.1-1017757.15. [10.3389/fmolb.2023.1017757]

The cyclic peptide G4CP2 enables the modulation of galactose metabolism in yeast by interfering with GAL4 transcriptional activity

S. Rosa
Co-primo
;
A. Tagliani
Co-primo
;
C. Bertaso;L. Tadini;C. Visentin;L.J. Gourlay;L. Feni;S. Pellegrino;P. Pesaresi;S. Masiero
Ultimo
2023

Abstract

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, able to interfere with the GAL4 protein, a transcription factor responsible for the activation of galactose catabolism in yeast and widely exploited in molecular biology. G4CP2 has been 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 limitation with respect to the target protein. The possible biotechnological applications of cyclic peptides are also discussed.
Gal4; Cyclic peptide; Combinatorial library; yeast two-hybrid; Protein interference; Galactose metabolism; Drug Discovery;
Settore BIO/01 - Botanica Generale
Settore BIO/18 - Genetica
Settore CHIM/06 - Chimica Organica
   Novel Pesticides for a Sustainable Agriculture (NoPest)
   NoPest
   EUROPEAN COMMISSION
   H2020
   828940

   Nuove strategie di difesa nei confronti del marciume nero della vite, una minaccia per la viticoltura lombarda (NO-BLACK)
   NO-BLACK
   REGIONE LOMBARDIA - Agricoltura
2023
1-mar-2023
hdl:2434/951956
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