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One of the strategies used by nature to regulate gene expression relies on the stimulicontrolled combination of DNA-binding proteins. This in turn determines the target-binding site within the genome, and thereby whether a particular gene is activated or repressed. Here we demonstrate how a designed basic region leucine zipper-based peptide can be directed towards two different DNA sequences depending on its dimerization arrangement. While the monomeric peptide is non-functional, a C-terminal metallo-dimer recognizes the natural ATF/CREB-binding site (5 0 -ATGA cg TCAT-3 0 ), and a N-terminal disulphide dimer binds preferentially to the swapped sequence (5 0 -TCAT cg ATGA-3 0 ). As the dimerization mode can be efficiently controlled by appropriate external reagents, it is possible to reversibly drive the peptide to either DNA site in response to such specific inputs. This represents the first example of a designed molecule that can bind to more than one specific DNA sequence depending on changes in its environment.

We report the synthesis and characterization of phototriggerable polymeric nanoparticles (NPs) for the intracellular delivery of small molecules and proteins to modulate cell activity. For that purpose, several photocleavable linkers have been prepared providing diverse functional groups as anchoring points for biomolecules.

We describe the first chemical synthesis of a functional mutant of the DNA binding domain of the oncoprotein MYC, using two alternative strategies which involve either one or two Native Chemical Ligations (NCLs).

No abstract