Biomolecular Computing - Bionanoelectronics: Bioinquiring and Bioinspired Devices - page 196

Cascading several gates is successful if the toehold-binding region of output
strands is protected in upstream gates. Translator gates, which consist of single-input
AND gates and convert the input to the output signal are useful in cascading circuits
that have different toehold and recognition sequences. If the output signal level is
not that required to act as input in the next operation, restoration can be achieved by
thresholding, implemented as a three-input AND gate, and amplification, based on
feedback reactions. The last gates prevented a 25% output leak in an 11-gate circuit,
but slowed the operation from 2 to 10 h.
Photonic Boolean computing with DNA aptamers has been demonstrated in
Yoshida and Yokobayashi ( 2007 ). These logic gates sense ssDNA molecules and
aptamer ligands (adenosine and thrombin) as inputs and generate fluorescent
signals as output. AND and OR logic gates have been implemented based on
the reversible structure-switching mechanism of signaling aptamers, based on the
equilibrium hybridization shift between an aptamer and a partially complementary
oligonucleotide in the absence or presence of a ligand.
Besides DNA-based logic gates, ribozyme-based gates working in solution
with short ssDNA strands as inputs have been extensively studied. Boolean logic
is implemented in this case by an appropriate cleavage of a fluorogenic sub-
strate sequence. For example, logic gates assembled from ligase units have been
reported in Stojanovic et al. ( 2005 ), the ligase processes being controlled by stem-
loop attachment. In another work, a molecular full-adder has been demonstrated
( Lederman et al. 2006 ), which consists of an array of seven stem-loop-controlled
deoxyribozyme-based logic gates using as inputs and three oligonucleotides and as
carry and sum outputs two fluorogenic cleavage/cutting reactions with green and
red emissions, respectively. Finally, a second-generation functional automaton able
to play a complete game of tic-tac-toe according to a perfect strategy has been
described in Macdonald et al. ( 2006 ). This medium-scale integrated automaton,
called MAYA-II (Molecular Array of YES and AND gates), consists of 128 stem-
loop-controlled deoxyribozyme-based logic gates, is operated by 32 oligonucleotide
input, and yields 8 two-channel fluorescent outputs across 8 wells. It is assembled
from three classes of logic gates: YESx, activated by one input, x; xANDy gates,
activated by two inputs, x and y; and xANDyAND-NOTz gates that require three
inputs, x, y, and z.
Another remarkable realization of biomolecular computing is the development
of a biomolecular keypad lock based on enzyme logic gates ( Strack et al. 2008 )
in which the output signals depend not only on the proper inputs but also on the
order in which these are introduced. This keypad is based on a model biochemical
reaction chain, represented schematically in Fig. 7.4 as a succession of three AND

sucrose

glucose

H 2 O 2

ABTS ox

INV

GOx

MP-11

Fig. 7.4 Biomolecular keypad