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Transcript
Available online at www.sciencedirect.com
ScienceDirect
Technological applications arising from the interactions of DNA
bases with metal ions
Ki Soo Park and Hyun Gyu Park
An intense interest has grown in the unique interactions of
nucleic acids with metal ions, which lead to the formation of
metal-base pairs and the generation of fluorescent
nanomaterials. In this review, different types of metal-base
pairs, especially those formed from naturally occurring
nucleosides, are described with emphasis also being given to
recent advances made in employing these complexes to
govern enzymatic reactions. The review also contains a
comprehensive description of DNA-templated inorganic
nanomaterials such as silver nanoclusters which possess
excellent fluorescence properties. Finally, a summary is given
about how these materials have led to recent advances in the
field of nanobiotechnology.
Address
Department of Chemical and Biomolecular Engineering (BK 21+
program), KAIST, Daehak-ro 291, Yuseong-gu, Daejeon 305-701,
Republic of Korea
Corresponding author: Park, Hyun Gyu ([email protected])
Current Opinion in Biotechnology 2014, 28:17–24
This review comes from a themed issue on Nanobiotechnology
Edited by Jonathan S Dordick and Kelvin H Lee
For a complete overview see the Issue and the Editorial
Available online 24th November 2013
0958-1669/$ – see front matter, # 2013 Elsevier Ltd. All rights
reserved.
Moreover, a large number of nucleic acid sequences
can be efficiently and cost-effectively generated by
employing automated solid-phase synthetic processes.
Finally, nucleic acids are highly stable entities that can
be manipulated under a wide range of environmental
conditions.
Metal ions, which have unique chemical and physical
properties related to electron conductivity, magnetism,
and catalysis, have been incorporated into nucleic acids to
create metal-mediated functioning materials [2]. A representative example is found in systems that use metal ions
rather than hydrogen-bond driven base pairing to
promote formation of base pairs between non-complementary DNA bases. This non-natural base pairing is
stabilized by coordination of metal ions to DNA bases.
Inorganic fluorescent nanomaterials such as silver
nanoclusters have attracted special interest as replacements for conventional organic fluorophores owing to their
desirable photophysical properties and high photostabilities. Among a number of synthetic routes developed to
prepare the inorganic fluorescent nanomaterials, those that
use nucleic acids, especially DNA, have been found to be
highly versatile [3]. As a result, DNA-mediated fluorescent
nanomaterials have been fabricated and extensively
applied in the development of novel bio-sensing strategies,
molecular logic gates, and nanomachines.
http://dx.doi.org/10.1016/j.copbio.2013.10.013
Introduction
Nucleic acids, polymers comprised of phosphodiester
linked chains of purine (adenine (A) and guanine (G))
and pyrimidine (thymine (T) and cytosine (C)) bases,
have long been recognized to be the carriers of genetic
information in living systems. However, in recent years
many attempts have been made to exploit the chemical
properties of nucleic acids in non-biological contexts.
Several desirable features of nucleic acids enable them
to be used to produce the nanomaterials and nanostructures [1]. For example, the sizes of nucleic acids are in
the nanometer range, with a duplex of ten nucleotides
having an overall length of 3.4 nm and a width of 2 nm.
In addition, nucleic acids undergo straightforward
sequence-dependent hybridization with complementary strands and they capture specific target molecules
with high specificities and affinities. This property
enables information to be conveniently and specifically
programmed into a variety of DNA nanostructures.
www.sciencedirect.com
The unique interactions of DNA bases with metal ions
have been utilized as the basis for the generation of metalbase pairs and fluorescent nanomaterials. In this review,
an overview of DNA-based metal-base pairs, especially
those formed by naturally occurring nucleosides, is given
along with a discussion of recent advances that have been
made in applications of these substances, including their
use to control enzymatic reactions. In addition, the synthesis, characterization and applications of DNA-templated fluorescent nanomaterials such as silver
nanoclusters are reviewed.
Metal ion-mediated base pairing
The metal ion-linked duplexes have attracted recent
interest because they possess metal-related properties
such as electron conductivity and magnetism, and they
can serve to govern interesting enzymatic reactions.
The first example of incorporation of metal ions into
the core of DNA double helixes was uncovered by Lee
et al. In this study, Lee et al. observed that the divalent
Current Opinion in Biotechnology 2014, 28:17–24
18 Nanobiotechnology
Figure 1
(a)
H
(d)
O
O
O
N
C
NH
HN
T
N
T
N
O
N
N
T
HgII
N
O
O
O
N
N
H
N
T
H
N
O
H
O
AgI
C
N
N
H
N
N
G
O
O
H
N
N
H
(b)
(e)
NH2
NH2
H2N
H2N
NH
C
N
N
C
N
C
N
O
N
N
C
AgI
N
O
O
N
PdC
O
(c)
O
T
H2N
AgI
T
NH
N
N
N
N
O
C
AgI
N
O
O
O
H2N
N
N
C
N
O
C
H2N
N
N
N
N
N
O
O
H2N
O
T
HgII
N
O
C
N
O
Current Opinion in Biotechnology
Schematic illustration of metal ion-mediated base pairing. (a) Hg2+ ion-mediated T–Hg2+–T pair formation [5]. (b) Ag+ ion-mediated C–Ag+–C pair
formation [6]. (c) Predicted structures of T–Ag+–C and T–Hg2+–C pairs [7,8]. (d) Ag+ ion-mediated base triplet CG.CAg+ [9]. (e) Predicted structure of
Ag+ ion-mediated PdC–Ag+–C pair [10,11]. PdC: pyrrolo-dC.
metal ions such as Zn2+, Co2+ and Ni2+ stabilize
unmodified DNA duplexes at elevated pH [4]. The
more direct observation of binding of metal ions in the
interiors of DNA duplexes was made in studies with
the naturally occurring thymine (T)–thymine (T) mismatched base pair, which demonstrated that Hg2+ ions
participate in formation of a stable T–Hg2+–T base
pair (Figure 1a) [5]. In a similar way, the natural
cytosine (C)–cytosine (C) mismatched base pair was
found to be stabilized by Ag+ ions through formation
of a C–Ag+–C base pair (Figure 1b) [6]. Also, Urata
et al. and Ono et al. independently discovered that a
duplex DNA containing a T–C mismatched base pair
is moderately stabilized in the presence of Ag+ and
Hg2+ ions, possibly as a result of the formation of
respective T–Ag+–C and T–Hg2+–C base pairs
(Figure 1c) [7,8]. Recently, Jyo et al. observed that
Current Opinion in Biotechnology 2014, 28:17–24
Ag+ ions mediate the formation of a DNA triplex
(CG.CAg+) by replacing Hoogsteen base pairing with
the metal-base pairing (Figure 1d) [9].
A fluorescent base analog, which is structurally similar
to the corresponding natural nucleobase and exhibits
environment-dependent fluorescence properties, was
also shown to form a metal ion-mediated base pair
[10]. In this effort, Park et al. found that when
pyrrolo-dC (PdC), a fluorescent analog of the cytosine
nucleobase, is paired with cytosine within a duplex
DNA, the fluorescence efficiency of PdC is significantly diminished in the presence of Ag+ ions
(Figure 1e) [11]. Park et al. assumed that Ag+ ions
stabilize the PdC–C mismatched base pair through
simultaneous coordination with the N3 nitrogen of
PdC and C. Formation of this complex leads to more
www.sciencedirect.com
Interactions of DNA bases with metal ions Park and Park 19
efficient pi-stacking of the mismatched nucleobases
and collisional quenching of the intrinsic fluorescence
of PdC.
Application of metal ion-mediated base
pairing
The novel techniques have been devised to detect Hg2+
and Ag+ ions by taking advantage of specific interactions
of these metal ions with the respective thymine–thymine
(T–T) and cytosine–cytosine (C–C) mismatched base
pairs (Figure 2a) [12,13]. In addition, new versions of
molecular beacon probes, consisting of hairpin-structured
DNA possessing fluorophore-quencher pairs at both ends,
have been constructed to monitor DNA hybridization and
to detect small molecules. The hydrogen bonding pattern
in the DNA stem region is replaced by metal-base pairing
(Figure 2b) [14,15]. The new molecular beacon was
demonstrated to be superior because it exhibits a lower
background signal, higher thermal stability, and more
flexible stem structures, all of which enable it to be more
applicable in complex biological environments. However,
the new molecular beacon probes still require double
labeling of DNA with a fluorophore and a quencher, a
requirement that leads to the need for more difficult
synthetic routes and a significant loss in the affinity
and specificity of the probe.
To overcome this limitation, several approaches have
been used to design label-free probes. In these strategies,
the molecular recognition events and signal generation
steps occur separately (Figure 2c) [16–18]. Representative of this approach is the design of a molecular beacon
probe that employs the complexes T–Hg2+–T or C–Ag+–
C to release Hg2+ or Ag+ from the DNA stem region upon
interaction with the target molecules. The released metal
ions then are employed to generate a signal, which
identifies the presence of the target molecules. By rationally designing the base sequence in the probes, this
simple label-free strategy can be employed to detect
various target molecules, such as complementary DNA,
proteins, and small molecules.
Metal ion-mediated base pairing has also been utilized to
construct DNA-based nanomolecular machines that are
capable of undergoing reversible and repeatable mechanical motion. Seminal studies by Sen et al. led to the development of a new three-way junction-based DNA
nanomachine, fueled by binding of Hg2+ ions to T–T
mismatches present in one of the three-way junction stems,
that exhibits reversible, mechanical and electrical switching (Figure 2d). Interestingly, this type of switching can be
employed to couple mechanical motion with changes in
hole transport efficiency, a feature which could facilitate
electrical monitoring of structural changes in DNA [19].
Finally, metal ion-mediated base pairing has also been
utilized to induce enzymatic reactions. The first example
www.sciencedirect.com
of this feature was uncovered by Urata et al., in a study
which demonstrated that, DNA polymerases in the presence of Hg2+ ions incorporate 20 -deoxy-thymidine 50 triphosphate (dTTP) at site opposite to thymine in a
template DNA. This process involves formation of a
stable T–Hg2+–T base pair and leads to elongation of
the primer and synthesis of a full-length product
(Figure 3a) [20]. At nearly the same time, Park et al.
described a Hg2+ and Ag+ promoted ‘illusionary’ polymerase activity that accomplishes an unnatural extension
reaction even at mismatched sites (T–T and C–C) of a
primer with template DNA (Figure 3b) [21]. These
workers utilized this unnatural polymerase activity
induced by metal ions as the basis for a novel strategy
to construct a molecular scale logic gate.
Recently, Urata et al. found that in the presence of Ag+
ions, adenine is mis-incorporated into the site opposite a
C residue in template DNA. This phenomenon probably
takes place through formation of a C–Ag+–A base pair
[22]. However, why a C–Ag+–A base pair instead of the
more thermodynamically stable C–Ag+–C base pair is
formed and, consequently, what is the molecular basis
of the Ag+-mediated incorporation of adenine remain
questions that do not have clear answers.
In addition to the induction of DNA polymerase activity,
metal ion-coordinated base pairing has been utilized to
trigger other enzymatic activities such as those of nicking
endonucleases (Figure 3c) [23], ligases (Figure 3d) [24],
and exonucleases [25]. The catalytic activities of some
deoxyribozymes, which are rationally modified to contain
T–T or C–C mismatched base pairs, have also been
modulated through formation of T-Hg2+-T or C-Ag+-C
base pairs [26,27]. In the same manner, Shangguan et al.
showed that the binding affinity of a DNA aptamer, which
is rationally modified to contain T–T mismatched base
pairs, can be controlled by Hg2+ ions through the formation of T–Hg2+–T [28].
DNA-templated fluorescent nanomaterials
Owing to the unique properties, which include high
fluorescence quantum yields, high photostabilities and
facile syntheses, fluorescent nanomaterials have emerged
as promising alternatives to conventional organic fluorophores [3]. A representative example of a fluorescent
nanomaterial of this type is a nucleic acid-templated
silver nanocluster consisting of a few to ten atoms of
silver (<2 nm). Nucleic acids, especially DNA, serve as
initial nucleation sites for fluorescent silver nanocluster
formation and they stabilize the clusters by serving as the
capping agents. The most common form of a DNA
template used to produce fluorescent silver nanoclusters
is the cytosine-rich single-stranded oligonucleotides [29],
but other nucleobases such as guanine and adenine have
also been reported to promote the formation of these
nanoclusters [30].
Current Opinion in Biotechnology 2014, 28:17–24
20 Nanobiotechnology
Figure 2
(a)
T-HgII-T
HgII
Electron
transfer
Graphene oxide
hv
C-AgI-C
AgI
Electron
transfer
Graphene oxide
hv
(b)
T-HgII-T
HgII
Target DNA
F
Q
(c)
T-HgII-T
HgII
Target DNA
QD
QD
HgII
(d)
h+
h+
X
HgII
FRET
FRET
T-HgII-T
Current Opinion in Biotechnology
Application of metal ion-mediated base pairing to the development of target-detecting strategies and DNA-based nanomachines. (a) Schematic
representation of the detection of heavy metal ions on the graphene oxide arrays [13]. (b) The use of stem flexibility to design metal ion-mediated
Current Opinion in Biotechnology 2014, 28:17–24
www.sciencedirect.com
Interactions of DNA bases with metal ions Park and Park 21
Figure 3
(a)
dTTP
w/o Hg2+
Klenow fragment
T
T
T
T
w/ Hg2+
T
(b)
DNA primer
HgII
T
DNA primer
T
T
C
C
Template DNA
X
X
Template DNA
: Taq DNA polymerase
T
HgII
: Taq DNA polymerase
C
T
: Hg2+
AgI
C
: Ag+
C
C
T
T
(c)
Recognition
sequence
T
T
T
C
T
A
G
G
w/ Hg2+
G
G
A
T
C
Nt. AlwI
T T
T T
T T
C
C
T
A
G
T
T
T
(d)
C
C
T
A
G
Cleavage site
T
T
w/ Hg2+
T
T
C
C
T
A
G
G
G
A
T
C
T T
T T
T T
+
Cleaved
DNA product
DNA ligase
T
T
DNA polymerase
dNTPs
C
C
w/ Ag+
DNA ligase
C
C
C
C
Rolling circle amplification
(RCA)
Current Opinion in Biotechnology
Application of metal ion-mediated base pairing to induce enzymatic activities. (a) Incorporation of thymine nucleotides by DNA polymerase through T–
Hg2+–T base pairing [20]. (b) ‘Illusionary’ polymerase activity triggered by Hg2+ and Ag+ ions via their interaction with T–T and C–C mismatched base
pair [21]. (c) Cleavage activity of nicking endonuclease triggered by Hg2+ ions, which form the stable T–Hg2+–T base pair [23]. (d) DNA ligase activity
induced by Hg2+ and Ag+ ions, which form corresponding stable T–Hg2+–T and C–Ag+–C base pairs [24].
Fluorescent silver nanoclusters have been also demonstrated to be efficiently generated from metal ion complexation with several secondary structures of DNA
including hairpin, G-quadruplex, triplex, and i-motif
(Table 1) [30–33]. Interestingly, double-stranded (ds)
DNAs, which are not regarded as good templates for
silver nanocluster generation [30], have been modified
so that they produce fluorescent silver nanoclusters.
Modified dsDNAs, which incorporate a loop moiety,
mismatched site, abasic site, and gap-site [34–37], have
been utilized as a synthetic template for fluorescent silver
nanocluster formation (Table 1).
(Figure 2 Legend Continued) molecular beacon probes that signal molecular interactions [14]. (c) Label-free metal ion-mediated molecular beacon
probe that operates by separating the molecular recognition and signal reporting steps [18]. (d) A three-way junction-based DNA nanomachine
exhibiting reversible, mechanical and electrical switching that is fueled by Hg2+ binding to T–T mismatched base pair [19].
www.sciencedirect.com
Current Opinion in Biotechnology 2014, 28:17–24
22 Nanobiotechnology
Table 1
Various types of DNA templates to promote formation of fluorescent silver nanoclusters
DNA structures
DNA sequences
0
0
lex/lem
Reference
Single-stranded linear DNA
5 -CCC TTT AAC CCC-3
50 -CCC TCT TAA CCC-30
50 -CCC TTA ATC CCC-30
50 -CCT CCT TCC TCC-30
50 -CCC TAA CTC CCC-30
350/485
420/520
470/572
530/620
650/705
[29]
DNA hairpin
50 -TATC CGT CCCCC ACG GATA-30 a
50 -TATC CGT GGGGG ACG GATA-30 a
50 -GGG TTA GGG T CCC CCC ACCC TTA CCC-30 a
581.7/646.3
544.6/614.6
494/570
581/646
[30]
G-quadruplex
50 -GGT GGT GGT GGT TGT GGT GGT GGT GG-30
325/420
510/680
[31]
DNA triplex
50 -GAG AGG AGA GAG AAG AGG AAG-30
30 -CTC TCC TCT CTC TTC TCC TTC-50
50 -CTC TCC TCT CTC TTC TCC TTC-30
480/534
[32]
i-motif
50 -(TAACCCC)4-30
50 -(CCCCAA)3CCCC-30
460/560
500/570
[33]
Duplex DNA with a six-cytosine loop
30 -CACG TGGA CTGA GG CCCCCC ACA CCT CTTC-50 b
50 -GTGC ACCT GACT CC TGT GGA GAAG-30
520/572
[34]
Duplex DNA with a mismatched site
30 -GGG ATT GGG X TTG GGA TTG GGA-50 c
50 -CCC TAA CCC T AAC CCT AAC CCT-30
520/570
[35]
Duplex DNA with an abasic site
30 -TAC CAC CCC CGT CGC-50
50 -ATG GTG GXG GCA GCG-30 d
588/670
[36]
Duplex DNA with a gap site
30 -CGA GTA CCA CCC CCG TCG CGG AG-50 e
50 -GCT CAT GGT GG-30
50 -GGC AGC GCC TC-30
560/643
[37]
a
b
c
d
e
The
The
The
The
The
[46]
underlined sequence is the stem region of hairpin structured DNA.
underlined sequence is the six-cytosine loop bulged from the duplex DNA.
underlined X is thymine, guanine, and cytosine nucleobases that is mismatched base paired with thymine in the opposite strand.
underlined X is the abasic site (dSpacer, tetrahydrofuran residue).
underlined C is the cytosine nucleobase that is positioned opposite the gap site within duplex DNA.
Application of DNA-templated fluorescent
nanomaterials
Various strategies that take advantage of the high fluorescence properties of DNA-silver nanoclusters have
been utilized to detect target DNA, microRNA,
proteins, small molecules, and metal ions [3]. A representative example is found in the discovery by Werner
et al. that the fluorescence of DNA-silver nanoclusters is
dramatically enhanced when particular nucleotides such
as guanine or thymine are placed in close proximity [38].
Based on this observation, these workers developed a
novel DNA detection probe, named a ‘Nano-Cluster
Beacon,’ that displays turn-on fluorescence upon target
binding. The same group also developed another type of
DNA probe, termed a ‘chameleon NanoCluster Beacon’
for the rapid and precise screening of single-nucleotide
polymorphisms (SNPs) [39]. This new molecular probe
consists of a silver nanocluster-containing strand and a
guanine-rich enhancer strand, which are brought into
close proximity when it binds to SNP targets. This
phenomenon brings about fluorescence emission at various wavelengths (colors) depending on the alignment
Current Opinion in Biotechnology 2014, 28:17–24
between silver nanoclusters and the enhancer. By following this approach, aptamer-based sensors have been
designed. These sensors rely on a target-induced conformational change of the DNA aptamer probe, containing silver nanoclusters, and guanine-rich enhancer
sequences at both ends. This change brings the guanine-rich enhancer sequence close to the silver nanoclusters and causes a resulting fluorescence enhancement
[40]. In addition, novel strategies for sensing biological
thiols such as cysteine, homocysteine, and glutathione
and metal ions such as Cu2+ and Hg2+ ions have been
devised based on the fact that these substances strongly
interact with and change the fluorescence of silver
nanoclusters [41–43].
DNA-silver nanoclusters have also been employed as
labeling systems for biomolecule imaging. Dickson
et al. initiated this area by designing DNA-protected
silver nanoclusters that are covalently conjugated with
avidin or a primary antibody for cell surface labeling [44].
Recently, it was also reported that the silver nanoclusters,
which specifically mark the nucleus of live cells, can be
www.sciencedirect.com
Interactions of DNA bases with metal ions Park and Park 23
prepared by using aptamers against target cells as the
nucleation template [45].
DNA-templated silver nanoclusters have been also
utilized to construct molecular logic gates, switches,
and fluorescent hydrogels that are applicable in the
area of nanobiotechnology. For example, Wang et al.
devised a molecular logic device, which employs K+ or
H+ ions as inputs and modulates the fluorescence properties of DNA-silver nanoclusters by inducing the structural changes in template DNA [46]. The same group
also designed a new type of fluorescent molecular
switch, which operates through a DNA strand exchange
reaction that leads to fluorescence on-off switching of
DNA-silver nanoclusters [47]. In addition, fluorescent
hydrogels, which are comprised of a Y-shaped DNA
structure modified with silver nanoclusters as a functional component, have been prepared and shown by
Willner et al. to exhibit thermally reversible solution–
hydrogel transitions without loss of fluorescence intensities [48].
Acknowledgements
This work was supported by the grant from the Basic Science and Public
Welfare & Safety Research Program through the National Research
Foundation of Korea (NRF) funded by the Ministry of Science, ICT and
Future Planning (No. 2009-0080602) (No. 2012M3A2A1051683) and the
Industrial Source Technology Development Program of the Ministry of
Knowledge Economy (MKE) (No. 2010-10038683).
References and recommended reading
Papers of particular interest, published within the period of review,
have been highlighted as:
of special interest
of outstanding interest
1.
Berti L, Burley GA: Nucleic acid and nucleotide-mediated
synthesis of inorganic nanoparticles. Nat Nanotechnol 2008,
3:81-87.
2.
Takezawa Y, Shionoya M: Metal-mediated DNA base pairing:
alternatives to hydrogen-bonded Watson–Crick base pairs.
Acc Chem Res 2012, 45:2066-2076.
3.
Latorre A, Somoza A: DNA-mediated silver nanoclusters:
synthesis, properties and applications. Chembiochem 2012,
13:951-958.
4.
Lee JS, Latimer LJ, Reid RS: A cooperative conformational
change in duplex DNA induced by Zn2+ and other divalent
metal-ions. Biochem Cell Biol 1993, 71:162-168.
5.
Miyake Y, Togashi H, Tashiro M, Yamaguchi H, Oda S, Kudo M,
Tanaka Y, Kondo Y, Sawa R, Fujimoto T et al.: MercuryIImediated formation of thymine-HgII-thymine base pairs in
DNA duplexes. J Am Chem Soc 2006, 128:2172-2173.
6.
Ono A, Cao S, Togashi H, Tashiro M, Fujimoto T, Machinami T,
Oda S, Miyake Y, Okamoto I, Tanaka Y: Specific interactions
between silver(I) ions and cytosine–cytosine pairs in DNA
duplexes. Chem Commun 2008:4825-4827.
7.
Urata H, Yamaguchi E, Nakamura Y, Wada S: Pyrimidine–
pyrimidine base pairs stabilized by silver(I) ions. Chem
Commun 2011, 47:941-943.
8.
Ono A, Torigoe H, Tanaka Y, Okamoto I: Binding of metal ions by
pyrimidine base pairs in DNA duplexes. Chem Soc Rev 2011,
40:5855-5866.
9.
Ihara T, Ishii T, Araki N, Wilson AW, Jyo A: Silver ion unusually
stabilizes the structure of a parallel-motif DNA triplex. J Am
Chem Soc 2009, 131:3826-3827.
Conclusions
Unique interactions between DNA bases and metal ions,
which lead to the formation of metal ion-mediated base
pairs and the generation of fluorescent nanomaterials,
have been used to construct novel sensing, imaging and
computing systems, and to build nanostructures and
nanomachines. Moreover, metal ion-mediated base pairing along with well-established sequence-specific
hybridization also has the potential of being employed
to produce complex DNA nanoarchitectures. In spite of
the substantial progress that has been made in exploring
the potential of specific interactions that take place
between DNA bases and metal ions, many challenges
remain. For example, the high specificities seen in metal
ion interactions with DNA bases have not been
explained fully because the formations of metal-base
pairs in most cases have only been indirectly confirmed
by observation of the enhanced thermal stabilities of the
corresponding duplexes. Owing to this gap, in-depth
investigations are required to fully understand the mechanism of metal ion binding to DNA bases. Furthermore,
the exact structures of silver nanoclusters have not been
unambiguously elucidated and, as a result, it is not
possible to generate a molecular basis to predict precisely
the emitting fluorescence, which has been observed to
depend on several variables, such as DNA sequence,
buffer, pH, and reagent concentration. Thus, additional
basic investigations are needed in order to determine
how the fluorescence properties of DNA-templated
nanomaterials can be more concisely controlled. Despite
these unsolved problems, it is expected that the development of more versatile metal-base pairs as well as
DNA-templated fluorescent nanomaterials will lead to
important breakthroughs in DNA-based biotechnologies
and nanotechnologies.
www.sciencedirect.com
10. Mei H, Röhl I, Seela F: Ag+-mediated DNA base pairing:
extraordinarily stable pyrrolo-dC–pyrrolo-dC pairs binding
two silver ions. J Org Chem 2013, 78:9457-9463.
11. Park KS, Lee JY, Park HG: Mismatched pyrrolo-dC-modified
duplex DNA as a novel probe for sensitive detection of silver
ions. Chem Commun 2012, 48:4549-4551.
12. Tao Y, Lin Y, Ren J, Qu XG: Self-assembled, functionalized
graphene and DNA as a universal platform for colorimetric
assays. Biomaterials 2013, 34:4810-4817.
13. Liu F, Ha HD, Han DJ, Seo TS: Photoluminescent graphene
oxide microarray for multiplex heavy metal ion analysis. Small
2013 http://dx.doi.org/10.1002/smll.201300499.
14. Yang R, Jin J, Long L, Wang Y, Wang H, Tan W: Reversible
molecular switching of molecular beacon: controlling DNA
hybridization kinetics and thermodynamics using mercury(II)
ions. Chem Commun 2009:322-324.
15. Wang Y, Li J, Wang H, Jin J, Liu J, Wang K, Tan W, Yang R: Silver
ions-mediated conformational switch: facile design of
structure-controllable nucleic acid probes. Anal Chem 2010,
82:6607-6612.
16. Ding J, Qin W, Zhang Y, Wang X: Potentiometric aptasensing
based on target-induced conformational switch of a DNA
probe using a polymeric membrane silver ion-selective
electrode. Biosens Bioelectron 2013, 45:148-151.
Current Opinion in Biotechnology 2014, 28:17–24
24 Nanobiotechnology
17. Liu JM, Yan XP: Competitive aptamer bioassay for selective
detection of adenosine triphosphate based on metal-paired
molecular conformational switch and fluorescent gold
nanoclusters. Biosens Bioelectron 2012, 36:135-141.
18. Wang Y, Li J, Jin J, Wang H, Tang H, Yang R, Wang K: Strategy for
molecular beacon binding readout: separating molecular
recognition element and signal reporter. Anal Chem 2009,
81:9703-9709.
19. Thomas JM, Yu HZ, Sen D: A mechano-electronic DNA switch. J
Am Chem Soc 2012, 134:13738-13748.
20. Urata H, Yamaguchi E, Funai T, Matsumura Y, Wada S:
Incorporation of thymine nucleotides by DNA polymerases
through T–HgII–T base pairing. Angew Chem Int Ed 2010,
49:6516-6519.
This is the first paper to report the enzymatic incorporation of metalmediated base pairs in DNA.
21. Park KS, Jung C, Park HG: ‘‘Illusionary’’ polymerase activity
triggered by metal ions: use for molecular logic-gate
operations. Angew Chem Int Ed 2010, 49:9757-9760.
This paper describes a new strategy in which a polymerase enzyme is
controlled to promote an unnatural extension reaction at the mismatched
site (T–T and C–C) of a primer with the template through the formation of
T–Hg2+–T and C–Ag+–C base pairs.
22. Funai T, Miyazaki Y, Aotani M, Yamaguchi E, Nakagawa O,
Wada S, Torigoe H, Ono A, Urata H: AgI ion mediated formation
of a C–A mispair by DNA polymerases. Angew Chem Int Ed
2012, 51:6464-6466.
This paper describes the enzymatic incorporation of C–Ag+–A base pair in
DNA.
23. Li F, Feng Y, Liu S, Tang B: Triggered activity of a nicking
endonuclease for mercuric(II) ion-mediated duplex-like DNA
cleavage. Chem Commun 2011, 47:6347-6349.
This paper describes an interesting finding that the cleavage activity of a
nicking endonuclease was triggered by T–Hg2+–T base pair.
24. Bi S, Ji B, Zhang Z, Zhu JJ: Metal ions triggered ligase activity
for rolling circle amplification and its application in
molecular logic gate operations. Chem Sci 2013, 4:18581863.
This paper describes an interesting finding that the ligase activity could be
triggered by T–Hg2+–T and C–Ag+–C base pair leading to the rolling circle
amplification.
25. Xuan F, Luo X, Hsing IM: Conformation-dependent exonuclease
III activity mediated by metal ions reshuffling on thymine-rich
DNA duplexes for an utrasensitive electrochemical method for
Hg2+ detection. Anal Chem 2013, 85:4586-4593.
26. Li T, Shi L, Wang E, Dong S: Silver-ion-mediated DNAzyme
switch for the ultrasensitive and selective colorimetric
detection of aqueous Ag+ and cysteine. Chem Eur J 2009,
15:3347-3350.
27. Qi L, Zhao Y, Yuan H, Bai K, Zhao Y, Chen F, Dong Y, Wu Y:
Amplified fluorescence detection of mercury(II) ions (Hg2+)
using target-induced DNAzyme cascade with catalytic and
molecular beacons. Analyst 2012, 137:2799-2805.
28. Mei H, Bing T, Qi C, Zhang N, Liu X, Chang T, Yan J, Shangguan D:
Rational design of Hg2+ controlled streptavidin-binding
aptamer. Chem Commun 2013, 49:164-166.
29. Richards CI, Choi S, Hsiang JC, Antoku Y, Vosch T, Bongiorno A,
Tzeng YL, Dickson RM: Oligonucleotide-stabilized Ag
nanocluster fluorophores. J Am Chem Soc 2008, 130:50385039.
30. Gwinn EG, O’Neill P, Guerrero AJ, Bouwmeester D, Fygenson DK:
Sequence-dependent fluorescence of DNA-hosted silver
nanoclusters. Adv Mater 2008, 20:279-283.
31. Ai J, Guo W, Li B, Li T, Li D, Wang E: DNA G-quadruplextemplated formation of the fluorescent silver nanocluster and
its application to bioimaging. Talanta 2012, 88:450-455.
32. Feng L, Huang Z, Ren J, Qu X: Toward site-specific,
homogeneous and highly stable fluorescent silver
Current Opinion in Biotechnology 2014, 28:17–24
nanoclusters fabrication on triplex DNA scaffolds. Nucleic
Acids Res 2012, 40:e122.
33. Sengupta B, Springer K, Buckman JG, Story SP, Abe OH,
Hasan ZW, Prudowsky ZD, Rudisill SE, Degtyareva NN, Petty JT:
DNA templates for fluorescent silver clusters and i-motif
folding. J Phys Chem C 2009, 113:19518-19524.
34. Guo W, Yuan J, Dong Q, Wang E: Highly sequence-dependent
formation of fluorescent silver nanoclusters in hybridized DNA
duplexes for single nucleotide mutation identification. J Am
Chem Soc 2010, 132:932-934.
35. Huang Z, Pu F, Hu D, Wang C, Ren J, Qu X: Site-specific DNAprogrammed growth of fluorescent and functional silver
nanoclusters. Chem Eur J 2011, 17:3774-3780.
36. Ma K, Cui Q, Liu G, Wu F, Xu S, Shao Y: DNA abasic site-directed
formation of fluorescent silver nanoclusters for selective
nucleobase recognition. Nanotechnology 2011, 22:305502.
37. Cui Q, Ma K, Shao Y, Xu S, Wu F, Liu G, Teramae N, Bao H: Gap
site-specific rapid formation of fluorescent silver
nanoclusters for label-free DNA nucleobase recognition. Anal
Chim Acta 2012, 724:86-91.
38. Yeh HC, Sharma J, Han JJ, Martinez JS, Werner JH: A DNA-silver
nanocluster probe that fluoresces upon hybridization. Nano
Lett 2010, 10:3106-3110.
This paper reports that the fluorescence of DNA-silver nanoclusters is
dramatically enhanced when the particular nucleotides such as guanine
or thymine are placed in proximity. On the basis of this observation, a
novel DNA detection probe named ‘Nano-Cluster Beacon’ that lights up
upon target binding is designed.
39. Yeh HC, Sharma J, Shih IM, Vu DM, Martinez JS, Werner JH: A
fluorescence light-up Ag nanocluster probe that discriminates
single-nucleotide variants by emission color. J Am Chem Soc
2012, 134:11550-11558.
This paper develops a new type of DNA probe, termed ‘chameleon
nanocluster beacon’, for the rapid and precise screening of singlenucleotide polymorphisms (SNPs) that lights up into different colors upon
binding to SNP targets.
40. Zhang M, Guo SM, Li YR, Zuo P, Ye BC: A label-free fluorescent
molecular beacon based on DNA-templated silver
nanoclusters for detection of adenosine and adenosine
deaminase. Chem Commun 2012, 48:5488-5490.
41. Huang Z, Pu F, Lin Y, Ren J, Qu X: Modulating DNA-templated
silver nanoclusters for fluorescence turn-on detection of thiol
compounds. Chem Commun 2011, 47:3487-3489.
42. Lan GY, Huang CC, Chang HT: Silver nanoclusters as
fluorescent probes for selective and sensitive detection of
copper ions. Chem Commun 2010, 46:1257-1259.
43. Guo W, Yuan J, Wang E: Oligonucleotide-stabilized Ag
nanoclusters as novel fluorescence probes for the highly
selective and sensitive detection of the Hg2+ ion. Chem
Commun 2009:3395-3397.
44. Yu J, Choi S, Richards CI, Antoku Y, Dickson RM: Live cell
surface labeling with fluorescent Ag nanocluster conjugates.
Photochem Photobiol 2008, 84:1435-1439.
45. Sun Z, Wang Y, Wei Y, Liu R, Zhu H, Cui Y, Zhao Y, Gao X: Ag
cluster-aptamer hybrid: specifically marking the nucleus of
live cells. Chem Commun 2011, 47:11960-11962.
46. Li T, Zhang L, Ai J, Dong S, Wang E: Ion-tuned DNA/Ag
fluorescent nanoclusters as versatile logic device. ACS Nano
2011, 5:6334-6338.
47. Guo W, Yuan J, Wang E: Strand exchange reaction modulated
fluorescence ‘‘off–on’’ switching of hybridized DNA duplex
stabilized silver nanoclusters. Chem Commun 2011, 47:1093010932.
48. Guo W, Orbach R, Mironi-Harpaz I, Seliktar D, Willner I:
Fluorescent DNA hydrogels composed of nucleic acidstabilized silver nanoclusters. Small 2013 http://dx.doi.org/
10.1002/smll.201300055.
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