The synthetic biology toolbox lacks
extendable and conformationally
controllable yet easy-to-synthesize building blocks that are long
enough to span membranes. To meet this need, an iterative synthesis
of α-aminoisobutyric acid (Aib) oligomers was used to create
a library of homologous rigid-rod 310-helical foldamers,
which have incrementally increasing lengths and functionalizable N-
and C-termini. This library was used to probe the inter-relationship
of foldamer length, self-association strength, and ionophoric ability,
which is poorly understood. Although foldamer self-association in
nonpolar chloroform increased with length, with a ∼14-fold
increase in dimerization constant from Aib6 to Aib11, ionophoric activity in bilayers showed a stronger length
dependence, with the observed rate constant for Aib11 ∼70-fold
greater than that of Aib6. The strongest ionophoric activity
was observed for foldamers with >10 Aib residues, which have end-to-end
distances greater than the hydrophobic width of the bilayers used
(∼2.8 nm); X-ray crystallography showed that Aib11 is 2.93 nm long. These studies suggest that being long enough to
span the membrane is more important for good ionophoric activity than
strong self-association in the bilayer. Planar bilayer conductance
measurements showed that Aib11 and Aib13, but
not Aib7, could form pores. This pore-forming behavior
is strong evidence that Aibm (m ≥ 10) building blocks can span bilayers.
A fundamental principle of digital computer operation is Boolean logic, where inputs and outputs are described by binary integer voltages. Similarly, inputs and outputs may be processed on the molecular level as exemplified by synthetic circuits that exploit the programmability of DNA base-pairing. Unlike modern computers, which execute large numbers of logic gates in parallel, most implementations of molecular logic have been limited to single computing tasks, or sensing applications. This work reports three G-quadruplex-based logic gates that operate simultaneously in a single reaction vessel. The gates respond to unique Boolean DNA inputs by undergoing topological conversion from duplex to G-quadruplex states that were resolved using a thioflavin T dye and gel electrophoresis. The modular, addressable, and label-free approach could be incorporated into DNA-based sensors, or used for resolving and debugging parallel processes in DNA computing applications.
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