DNA-Based Nanodevices Controlled by Purely Entropic Linker Domains

Abstract

We demonstrate here the rational design of purely entropic domains as a versatile approach to achieve control of the input/output response of synthetic molecular receptors. To do so and to highlight the versatility and generality of this approach, we have rationally re-engineered two model DNA-based receptors: a clamp-like DNA-based switch that recognizes a specific DNA sequence and an ATPbinding aptamer. We show that, by varying the length of the linker domain that connects the two recognition portions of these receptors, it is possible to finely control their affinity for their specific ligand. Through mathematical modeling and thermodynamic characterization, we also demonstrate for both systems that entropy changes associated with changes in linker length are responsible for affinity modulation and that the linker we have designed behaves as a disordered random-coil polymer. The approach also allows us to regulate the ligand concentration range at which the receptors respond and show optimal specificity. Given these attributes, the use of purely entropic domains appears as a versatile and general approach to finely control the activity of synthetic receptors in a highly predictable and controlled fashion.

Conformational Entropy as a Means to Control the Behavior of Poly(diketoenamine) Vitrimers In and Out of Equilibrium

“…Moreover,t his dynamic behavior appears to be controllable at the level of monomers,a sthese choices set forth the energy landscapes available to the system to reconfigure.R elated effects tied to conformational entropy have been seen in loop formation elsewhere,f or example in multivalent and intramolecular ligand-receptor interactions. [29][30][31][32] We further evaluated the impact of network microstructure on how PDK vitrimers flow for architecturally similar networks by determining,v ia the Maxwell relation, the topology freezing transition temperature (T v ), which relates the temperature at which the vitrimersv iscosity increases above h = 10 12 Pa s. Forall PDK vitrimers, T v < T g ,indicating that the topology of network remains frozen below T g even though bond exchange reactions are,inp rinciple,allowed. It is further notable that T v decreased from À20 8 8CtoÀ45 8 8Cas the TMHDAl oading was increased from 20 %t o6 0%, whereas it increased from À1 8 8Cto118 8Casthe IPDAloading was increased from 20 %t o6 0% (Supporting Information, Table S3).…”

Independent Control of the Thermodynamic and Kinetic Properties of Aptamer Switches

“…Since hairpin hybridization strength confers coarse-grained control over binding affinity 14 and linker length confers fine-grained control of binding thermodynamics 15 , the incorporation of both tuning mechanisms makes this switch design highly amenable to the fine-tuning of molecular recognition ( Fig. 2a).…”

Conformational Entropy as a Means to Control the Behavior of Poly(diketoenamine) Vitrimers In and Out of Equilibrium

“…Moreover, this dynamic behavior appears to be controllable at the level of monomers, as these choices set forth the energy landscapes available to the system to reconfigure. Related effects tied to conformational entropy have been seen in loop formation elsewhere, for example in multivalent and intramolecular ligand–receptor interactions …”