Towards regulation of peptide-DNA interaction using an allosteric molecule

QUIROLO ZULMA BEATRIZ; JOSÉ L. MASCAREÑAS; DODERO V. I

Carlos Paz

Congreso; SAB 2013; 2013

Sociedad Argentina de Biofísica

Cells receive a wide variety of cellular and environmental signals which must be processed to generate specific and timely genetic responses. The first step in the expression of genetic information, namely the synthesis of RNA from DNA template, is tightly regulated by DNA-binding proteins called Transcription factors (TFs). One of them, is GNC4, a TFs found in yeast which recognizes it cognate DNA binding domain as a helical dimer. The structural motif is composed by two regions: one responsible of recognition named the basic region and the other is the leucine zipper domain responsible of dimerization. Previously, we have used this model peptide to prove spatial and temporal control [1, 2]. Now, we envisaged the use of a truncated GNC4 peptide which possesses only the basic region chemically modified at the N-terminal in order to promote dimerization and DNA recognition in the presence of an allosteric molecule. This molecule possesses two β-Cyclodextrins to promote peptide dimerization and a linker based on an azobenzene moiety which is able to change its conformation upon light irradiation. The chemical synthesis, structural characterization and the initial binding experiments are presented. Acknowledgements: Supported by UNS, CONICET, DAAD, and ME-SPU (17-16-296) grants. References: 1-             Blanco J. B.; Dodero V. I.; Vázquez M. E.; et.al Angew. Chem. Int. Ed. 2006, 118, 8390. Mosquera, J.; Jiménez-Balsa, A.; Dodero, V. I.; Vázquez, M. E.; Mascareñas, J. L. Nature Comm, 2013, 4, 1874