ja501859w_si_001.pdf (695.03 kB)
Rational Design of Highly Responsive pH Sensors Based on DNA i‑Motif
journal contribution
posted on 2014-06-25, 00:00 authored by Irina V. Nesterova, Evgueni E. NesterovAvailability of strategies
for molecular biosensing over a finely
adjustable dynamic range is essential for understanding and controlling
vital biological processes. Herein we report design principles of
highly responsive pH sensors based on a DNA i-motif where both response
sensitivity and transition midpoint can be tuned with high precision
over the physiologically relevant pH interval. The tuning is accomplished
via rational manipulations of an i-motif structure as well as incorporation
of allosteric control elements. This strategy delivers molecular sensing
systems with a transition midpoint tunable with 0.1 pH units precision
and with a total response range as narrow as 0.2 pH units which can
be adjusted to a variety of outputs (e.g., fluorescent readout). The
potential of the presented approach is not limited by pH sensing but
may extend toward manipulation of other quadruplex based structures
or the development of ultraresponsive elements for artificial molecular
machines and signaling systems.