Here we report a rational strategy to orthogonally control assembly and disassembly of DNA-based nanostructures using specific IgG antibodies as molecular inputs. We first demonstrate that the binding of a specific antibody to a pair of antigen-conjugated split DNA input-strands induces their co-localization and reconstitution into a functional unit that is able to initiate a toehold strand displacement reaction. The effect is rapid and specific and can be extended to different antibodies with the expedient of changing the recognition elements attached to the two split DNA input-strands. Such an antibody-regulated DNA-based circuit has then been employed to control the assembly and disassembly of DNA tubular structures using specific antibodies as inputs. For example, we demonstrate that we can induce self-assembly and disassembly of two distinct DNA tubular structures by using DNA circuits controlled by two different IgG antibodies (anti-Dig and anti-DNP antibodies) in the same solution in an orthogonal way.

A kinetic study on the reactions of the cumyloxyl radical (CumO) with N-Boc-protected amino acids in the presence of the strong organic base DBU has been carried out. COH deprotonation increases the electron density at the α-C-H bonds activating these bonds toward HAT to the electrophilic CumO strongly influencing the intramolecular selectivity. The implications of these results are discussed in the framework of HAT-based aliphatic C-H bond functionalization of amino acids and peptides.

The function and activity of many proteins is finely controlled by the modulation of the entropic contribution of intrinsically disordered domains that are not directly involved in any recognition event. Inspired by this mechanism we demonstrate here that we could finely regulate the catalytic activity of a model DNAzyme (i.e. a synthetic DNA sequence with enzyme-like properties) by rationally introducing intrinsically disordered nucleic acid portions in its original sequence. More specifically, we have re-engineered here the well-characterized Cu 2+ -dependent DNAzyme that catalyses a self-cleavage reaction by introducing a poly(T) linker domain in its sequence. The linker is not directly involved in the recognition event and connects the two domains that fold to form the catalytic core. We demonstrate that the enzyme-like activity of this re-engineered DNAzyme can be modulated in a predictable and fine way by changing the length, and thus entropy, of such linker domain. Given these attributes, the rational design of intrinsically disordered domains could expand the available toolbox to achieve a control of the activity of DNAzymes and, in analogy, ribozymes through a purely entropic contribution.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

We report here the rational design and optimization of an antibody-responsive, DNA-based device that enables communication between pairs of otherwise non-interacting proteins. The device is designed to recognize and bind a specific antibody and, in response, undergo a conformational change that leads to the release of a DNA strand, termed the "translator," that regulates the activity of a downstream target protein. As proof of principle, we demonstrate antibodyinduced control of the proteins thrombin and Taq DNA polymerase. The resulting strategy is versatile and, in principle, can be easily adapted to control protein-protein communication in artificial regulatory networks.The complex, tightly regulated networks [1,2] through which DNA, RNA and proteins interact underly the functioning of living systems. [3][4][5] One of the aims of synthetic biology is to create artificial pathways in which DNA, RNA and proteins interact with each other via analogously "programmed" reaction patterns to create new tools for sensing, drugdelivery, cell imaging. [6][7][8][9][10][11][12][13][14] A widely used approach to this end is the rational design of synthetic DNA/protein communication that takes advantage of the many naturally occurring proteins that recognize and bind specific oligonucleotide sequences to, for example, regulate transcription or translation. [15][16][17][18][19][20][21] Such sequence-specific recognition has been employed in synthetic systems to regulate the load/release of molecular cargos from DNA-based devices, [22] the assembly/ disassembly of DNA-based structures [23] and DNA-based reactions. [24]