Light-triggered capture and release of DNA and proteins by host-guest binding and electrostatic interaction

Article abstract of DOI:10.1002/chem.201405936

The development of an effective and general delivery method that can be applied to a large variety of structurally diverse biomolecules remains a bottleneck in modern drug therapy. Herein, we present a supramolecular system for the dynamic trapping and li

Full text of DOI:10.1002/chem.201405936

DOI: 10.1002/chem.201405936
Full Paper
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Self-Assembly |Hot Paper|
Light-Triggered Capture and Release of DNA and Proteins by
Host–Guest Binding and Electrostatic Interaction
Johanna Moratz, Avik Samanta, Jens Voskuhl, Siva Krishna Mohan Nalluri, and
Bart Jan Ravoo*[a]
Abstract: The development of an effective and general de-
livery method that can be applied to a large variety of struc-
turally diverse biomolecules remains a bottleneck in modern
drug therapy. Herein, we present a supramolecular system
for the dynamic trapping and light-stimulated release of
both DNA and proteins. Self-assembled ternary complexes
act as nanoscale carriers, comprising vesicles of amphiphilic
cyclodextrin, the target biomolecules and linker molecules
with an azobenzene unit and a charged functionality. The
non-covalent linker binds to the cyclodextrin by host–guest
complexation with the azobenzene. Proteins or DNA are
then bound to the functionalized vesicles through multiva-
lent electrostatic attraction. The photoresponse of the host–
guest complex allows a light-induced switch from the multi-
valent state that can bind the biomolecules to the low-affini-
ty state of the free linker, thereby providing external control
over the cargo release. The major advantage of this delivery
approach is the wide variety of targets that can be ad-
dressed by multivalent electrostatic interaction, which we
demonstrate on four types of DNA and six different proteins.
Introduction
In the past, we have established vesicles of amphiphilic cy-
clodextrin (CDV) as a versatile platform for the display of func-
tional guests on the membrane surface.[12] For this purpose, cy-
clodextrins (CDs) are equipped with long, hydrophobic alkyl
chains and hydrophilic oligo(ethyleneglycol) head groups. The
resulting amphiphiles can be cast into thin films via evapora-
tion from organic solvent, stirred with aqueous buffer and ex-
truded through a polycarbonate membrane. This procedure
yields unilamellar bilayer vesicles with about half of the macro-
cycles present on the outside of the CDV (Scheme 1). The cavi-
ties of CD are accessible for guest molecules, for example, azo-
benzene, which in turn can be modified with other functionali-
ties to build up complex supramolecular structures. Azoben-
zenes are especially interesting guest molecules, given that
they can be isomerized by UV irradiation at 350 nm from the
trans-isomer, which binds to CD, to cis-azobenzene, which
does not. This unique feature has been used for the generation
of light-responsive vesicles,[13] microcapsules and mesoporous
nanoparticles,[14] organogels[15] and hydrogels,[16] surfaces,[17]
supramolecular polymers,[18] and for catalyst-activity control.[19]
Our group has recently described the supramolecular complex-
ation and release of polyanionic DNA by using CDV and azo-
benzene-spermine conjugates.[20] We could also show that azo-
benzene–carbohydrate guest molecules could mediate the
self-assembly of ternary complexes with CDV and lectins
through specific interactions between carbohydrates and
proteins.[21]
Physiological processes in living organisms are regulated by
small molecules, as well as large biomacromolecules.[1] Classic
drug therapy focuses on relatively simple organic molecules
due to the easier synthetic access and higher bioavailability,
but over the last 30 years, the importance of biopharmaceuti-
cals has steadily increased.[2] Peptides and proteins already
serve as powerful drugs, but their low in vivo stability remains
an unsolved problem.[3] To harness the full therapeutic poten-
tial of these potent molecules, an effective and universal trans-
porter system is required. Recent advances in this area are pri-
marily based on polymer hydrogels and nanogels.[4] Other ex-
amples of stimuli-responsive protein delivery systems include
nanocapsules based on a pH-degradable polymeric shell,[5]
nanostructured lipid carriers,[6] and polyelectrolyte nanoparti-
cles.[7] Another challenge in modern medicine is gene therapy
by transfection of DNA and RNA. In this case, a delivery system
is essential to enable cellular uptake of the nucleic acids and
protect them from hydrolysis and enzymatic decomposition.
Promising artificial vectors include polyionic supramolecular
complexes (“polyplexes”) of DNA with corresponding polycat-
ions.[8] Cargo release was realized in response to pH,[9] reduc-
tion potential,[10] or light.[11]
[a] J. Moratz, A. Samanta, Dr. J. Voskuhl, Dr. S. K. Mohan Nalluri,
Prof. Dr. B. J. Ravoo
Organic Chemistry Institute and Graduate School of Chemistry
Westfꢀlische Wilhelms-Universitꢀt Mꢁnster
Corrensstrasse 40, 48149 Mꢁnster (Germany)
E-mail: b.j.ravoo@uni-muenster.de
Herein, we combine and expand these two strategies into
a supramolecular system for the capture and release of DNA
and proteins based on a combination of orthogonal host–
guest complexation and electrostatic interaction. Heterobifunc-
tional linker molecules 2–5, containing an azobenzene guest
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201405936.
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described in the Supporting In-
formation. The conjugates 2, 2’,
and 5 consist of an azobenzene
unit and
a charged moiety,
which is either spermine or a di-
peptide of glutamic acid, con-
nected through
a
hydrophilic
spacer.
tetra(ethyleneglycol)
Linker molecule 2’ was used in
previous studies and results are
shown for comparison. Linker
molecule 2 is more straightfor-
ward to prepare and was used
for all further experiments. Mole-
cule 3 carries a spermine moiety
linked to an azobenzene func-
tionality without a spacer. Finally,
linker
4 comprises guanidine
and azobenzene moieties, con-
nected through a short di(ethy-
leneglycol) spacer.
The azobenzene unit of the
heterobifunctional linker mole-
cules 2–5 is known to form
light-responsive inclusion com-
plexes with CDV.[22] By irradiation
with UV light, CD-binding trans-
azobenzene can be transformed
into the polar, bent cis-isomer,
which does not bind to CD.
However, cis-azobenzene dis-
plays a local absorption maxi-
mum around 350 nm, and there-
fore, the re-isomerization to the
trans-isomer is also promoted by
Scheme 1. Schematic illustration of cyclodextrin vesicles and structures of host and guest molecules used in this
study. 1: Amphiphilic a-cyclodextrin; 2: azobenzene spermine conjugate with tetra(ethyleneglycol) spacer; 3: azo-
benzene spermine conjugate; 4: azobenzene guadinium conjugate; and 5: azobenzene tricarboxylate with tetra-
(ethyleneglycol) spacer.
unit and a charged functionality, selectively bind both CDV and
charged biomolecules. The conformation of the azobenzene
and thus the formation of host–guest inclusion complexes can
be controlled by UV irradiation. Ultimately, this leads to light-
responsive aggregation or displacement of proteins and DNA.
We optimized complexation and investigated the impact of
multivalency by probing the influence of the spacer and the
charged moiety in the linker molecule. We also explored the
effect of the biomolecule target and its charge distribution by
testing DNA strands of different length, as well as multiple pro-
teins with different pI values. To this end, we employed opti-
cal-density measurements at l=600 nm (OD600), dynamic light
scattering (DLS), and z-potential measurements. The interac-
tion between CD and linker molecules was confirmed by iso-
thermal titration calorimetry (ITC).
UV irradiation. As a consequence, exposure to UV light leads to
a so-called photostationary state, in which both isomers exist
in dynamic equilibrium. The photoisomerization of 2–5 is
shown in Figures S1–S4 in the Supporting Information. The
binding to CD was confirmed by ITC and results are shown in
Figures S14–S16 in the Supporting Information. The binding
constants of azobenzene for CDV are slightly reduced com-
pared to unmodified a-CD (Ka ꢀ6ꢁ103 mÀ1) due to steric hin-
drance of host–guest interaction by the oligo(ethyleneglycol)
residues, present on the vesicle surface.[12b]
The trapping of DNA and proteins is realized by electrostatic
interaction of the charged moiety incorporated in the linker
molecules with anionic or cationic residues on the biomole-
cules. Despite the low affinity of a single binding unit, com-
plexation proceeds readily due to multivalent interaction of
the biomolecule with multiple linker molecules bound to the
same vesicle. CDV functionalized with heterobifunctional link-
ers should therefore act as supramolecular “adhesive”, captur-
ing oppositely charged target molecules in a ternary complex.
Photoisomerization of the azobenzene moiety in the linker
molecules from trans to cis should then lead to dissociation of
the host–guest complex, thereby switching from a multivalent
Results and Discussion
The synthesis of amphiphilic a-CD 1 was carried out as de-
scribed previously.[12b] Unilamellar vesicles with a diameter of
100 nm were prepared by extrusion in aqueous buffer (pH 7.2).
The synthesis and characterization of linker molecules 2–5 is
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Scheme 2. Schematic presentation of the electrostatic aggregation of guest
decorated cyclodextrin vesicles induced by “cationic” proteins (left) and
“anionic” proteins or DNA (right).
display of binding sites on the vesicle surface to a state of low-
affinity monovalent interaction of the free linker (Scheme 2).
We recently applied this strategy for the supramolecular trap-
ping and photoresponsive release of polyanionic single strand-
ed DNA comprising 50 nucleotides (50-mer ssDNA) with CDV
and positively charged linker molecule 2’.[20] In contrast, under
the same conditions double stranded DNA (dsDNA, 2000 bp)
could only be captured, but light-controlled dissociation of the
ternary complex was not feasible.[20]
Figure 1. Light-responsive aggregation and dissociation of ternary com-
plexes. A) Time-dependent OD600 measurements. B) Size distribution by DLS.
C) Light-induced dissociation of the complex. Concentrations: [1]=30 mm;
[2]={20, 30, 40, 60} mm, [25-mer DNA]=2.6 mm, [50-mer DNA]=0.7 mm,
[100-mer DNA]=0.6 mm, [dsDNA]=40 nm.
Encouraged by these results, we investigated this system in
more detail. To explore the effect of the DNA length on the ag-
gregation and release, we subjected single stranded 25-mer
and 100-mer oligonucleotides to the same conditions. Addition
of DNA to a mixture of CDV and 2 in aqueous buffer caused an
immediate increase in OD600 (Figure 1A) and particle size in-
creased from 100 to about 1000 nm (Figure 1B). The rate and
degree of aggregation can be altered by changing the concen-
tration of the linker. At high concentration, rapid and extensive
aggregation was observed, whereas aggregation was much
slower and gave a lower final OD600 at low concentration (data
shown for 25-mer and 100-mer DNA in Figure S5 in the Sup-
porting Information). Binary mixtures lacking one of the com-
ponents did not show any aggregation.[20] These results imply
that in the presence of CDV, linker 2 can induce the formation
of ternary supramolecular complexes with DNA strands of dif-
ferent lengths. We then investigated the photoresponsiveness
of these complexes. For the single-stranded DNAs, irradiation
of the ternary mixtures for 40 min at 350 nm lead to a decrease
in particle diameter from roughly 1000 to 100 nm (Figure 1B),
and the optical density was reduced to about 0.05, corre-
sponding to the value for free vesicles (Figure 1C). In contrast,
we recently reported that OD600 and particle size remained
high when double-stranded DNA was irradiated under the
same conditions (Figure S6 in the Supporting Information).[20]
These findings suggest that within certain size limits, oligonu-
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cleotides can be captured and released independent on their
length. Exceeding this limit, the double stranded DNA can be
trapped in the supramolecular complex, but photoinduced dis-
sociation does not occur.
Supporting Information). The highly negative surface potential
of bare CDV (À26 mV) increased to +3.2 mV when the vesicles
were decorated with 3, which is less positive than the surface
potential previously detected for CDV covered with linker 2’
(+11 mV). In contrast to 2’, linker 3 is lacking the tetra(ethyle-
neglycol) spacer. It is reasonable to assume that the spacer
allows the spermine groups of 2’ to reach away from the CDV
so that they are exposed to the aqueous medium and accessi-
ble for DNA. Evidently, the spacer causes a higher z-potential
and enables stronger interaction with the negatively charged
binding partner. The lack of a spacer in 3 prevents the effective
display of positive charges and the negative surface potential
of the CDV prevails, leading to repulsion of the polyanionic
DNA. Additionally, it should be considered that without the
spacer, the binding sites for DNA are displayed rather rigidly
and close to the vesicle surface. It can be assumed that this
allows binding of ssDNA only, since this target is shorter and
more flexible than the dsDNA.
These results can be explained by the fact that host–guest
complexation with CDV is only possible with trans-azobenzene.
Irradiation with UV-light causes photoisomerization into the
cis-isomer, which is not a suitable guest for CDV and therefore
dissociates from the vesicles. This leads to the above-men-
tioned loss of multivalency and thus to release of the ssDNA.
Nevertheless, a small amount of trans-azobenzene is still pres-
ent in the photostationary state. Although this amount is not
sufficient to effectively bind the shorter oligonucleotides, the
larger dsDNA can still complex several linker molecules on the
same vesicle, forming a stable multivalent complex. Our find-
ings thereby illustrate the crucial role of multivalency in this
system.
To get deeper insight into the system and optimize com-
plexation, we then focused our interest on the influence of the
linker molecule. Having shown that the aggregation and re-
lease of the tested single-stranded DNAs is comparable, we se-
lected 50-mer ssDNA and dsDNA for that purpose. Figure 2
Upon applying linker 4 instead of linker 2 or 3, no agglutina-
tion was observed for either ssDNA or dsDNA. The OD600 of the
ternary mixtures remained as low as 0.01 (Figure 2). The parti-
cle size of 100 nm, measured by DLS, corresponds to the free
CDV (Figure S7 in the Supporting Information). These results il-
lustrate the effect of the protein-binding moiety. In a ternary
mixture comprising CDV and 2’, both DNA samples form supra-
molecular complexes leading to an increase in OD600. Com-
pared to 2’, linker 4 comprises a guanidine unit instead of
a spermine. Under the tested conditions (pH 7.2), the guani-
dine is mostly unprotonated and thus not charged. This was
confirmed by the negative surface potential of À14.8 mV re-
corded for CDV after addition of 4 (Figure S8 in the Supporting
Information). As a result, this linker should bind to the phos-
phate backbone of DNA by hydrogen bonding with guanidine
rather than by electrostatic interaction. Interestingly, no aggre-
gation was observed, indicating that the DNA cannot bend
into the confined geometry that would be needed for multiva-
lent hydrogen bonding. These results indicate that the lack of
directionality in the electrostatic interaction between DNA and
linker molecules 2’ and 3 is crucial for the formation of a supra-
molecular complex.
Figure 2. Time-dependent measurement of OD600 showing the formation of
ternary complexes of DNA and CDV with linker molecules 2’–4; Concentra-
tions: [1]=30 mm; [2’]={40, 60} mm; [3]=[4]=60 mm; [50-mer DNA]={1.6,
3.2} mm, [dsDNA]=40 nm.
In the second part of this study, we expand the scope of
target biomolecules from DNA to proteins. As positively
charged linker molecule we selected 2, which gave the best re-
sults in the experiments with DNA. Linker 5 was synthesized
for these studies with the same azobenzene and spacer unit,
bearing a dipeptide of glutamic acid instead of the spermine.
In a first set of experiments, we tested bovine serum albumin
(BSA, pI=4.7), bearing a net negative charge of À15 in combi-
nation with cationic linker 2 and polycationic protamine sulfate
(PS, pI=13.3) with a total charge of +20 in combination with
anionic linker 5 (Figure 3).
An increase in OD600 from 0.05 to about 1.0 was detected
for ternary mixtures when protein and linker were oppositely
charged, whereas other combinations resulted in no aggrega-
tion. The rate and extent of aggregation are controlled by the
concentration of the linker: instant and complete agglutination
occurred at high concentrations, whereas at low concentration,
shows the OD600 of ternary mixtures of CDV and DNA with dif-
ferent linkers (2’–4). In the case of linker molecule 3, only
ssDNA showed aggregation and consequently an increase in
optical density from 0.01 to about 0.91, which is comparable
to the results with linker 2’ discussed above. Under the same
conditions, dsDNA did not display substantial aggregation:
OD600 increased to only 0.07. The aggregation was also fol-
lowed by DLS (Figure S7 in the Supporting Information). The
average particle diameter increased from about 100 nm for the
free vesicles to more than 1000 nm after addition of 50-mer
DNA. In contrast, the particle diameter was unaffected by addi-
tion of dsDNA. Finally, measurements of the zeta potential
were carried out (shown for 50-mer DNA in Figure S8 in the
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duced rapid recovery of the original particle size for free CDV
of 100 nm (Figure 4A). Dissociation proceeded within two mi-
nutes of irradiation, illustrated by the decrease in OD600 (Fig-
ure S10 in the Supporting Information).
To prove that our concept could be applied to a variety of
target proteins, comparative studies with six different proteins
were conducted. Out of these, five proteins showed orthogo-
nal aggregation with respect to the total charge of the respec-
tive protein and linker (see Figure S11/Table 1 in the Support-
ing Information). Among the tested proteins, only mono-amine
oxidase A (pI=7.9) was not bound, which can be attributed to
its near neutral overall charge. However, horse radish perox-
idase (pI=6.8) showed aggregation, implying that local charge
distribution on the protein surface and accessibility of the
charged residues for the linkers could affect the extent of elec-
trostatic binding. In conclusion, these results provide clear-cut
evidence that proteins can be captured and released from
a supramolecular, light-responsive complex. Protein capture is
selective with respect to the overall protein charge and can be
applied to a variety of target proteins.
Figure 3. Formation of ternary complexes with proteins: Time-dependent
OD600 measurements. Concentrations: [1]=100 mm; [linker]=50 mm; [pro-
tein]=15 mm.
The importance of electrostatic interaction for DNA and pro-
tein capture was verified by addition of NaCl and competitive
binder spermine·4HCl to a ternary mixture of CDV, 2, and 50-
mer DNA or BSA, respectively. As was described above, DNA
was bound in the presence of 150 mm NaCl and OD600 conse-
quently increased from 0.01 to about 0.86 (Figure 1A). Howev-
er, even in the presence of only 50 mm NaCl, BSA displayed no
substantial aggregation and OD600 remained as low as 0.03
(Figure S12 in the Supporting Information). This can be attrib-
uted to the effective display of negative charges on the DNA,
which is an elongated, rod-like molecule. The phosphate
groups of the DNA backbone are exposed into the surround-
ing medium and are easily accessible for electrostatic interac-
tion with the linker. In contrast, in the case of BSA, not all
charges are available for complexation due to protein folding.
Additionally, local electrostatic repulsion of the positively
charged linker by positively charged amino acids in the protein
can occur. As a consequence, the monovalent Na+ can com-
pete with the trivalent spermine linker only in the case of the
protein, in which the interaction with the spermine is weaker
compared to DNA. However, when the preformed protein
complexes were treated with 50 mm NaCl, OD600 only de-
creased to 0.6 implying that the aggregates remained partly
intact (Figure S13 in the Supporting Information). To trigger
complete release of the DNA, treatment of the ternary com-
plex with competitive tetravalent binder spermine·4HCl
(50 mm) was performed. This molecule is able to displace the
linker molecule 2 despite its lower affinity for the DNA, due to
the much higher concentration. Consequently, the ternary
complex disassembles and the OD600 decreases because sper-
mine does not bind to CDV. Taken together, these results con-
sistently support the concept of biomolecule trapping by elec-
trostatic interaction with the heterobifunctional linker
molecules.
Figure 4. Light-responsive formation and dissociation of ternary complexes
with proteins; A) Size distribution by DLS. B) Zeta-potential measurements at
258C. Concentrations: [1]=100 mm; [linker]=50 mm; [BSA]=1.5 mm; [prota-
mine sulfate]=15 mm.
aggregation was observed to a lesser extent and also much
slower (Figure S9 in the Supporting Information). Upon aggre-
gation, the mean particle diameter increased from 100 to
400 nm for PS and to 4000 nm in the case of BSA (Figure 4A).
The resulting complexes were subjected to UV light (l=
350 nm) for 25 minutes. Photoisomerization of the linker in-
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UV/Vis spectroscopy
Conclusion
Capture and release of DNA and proteins was achieved in self-
assembled ternary complexes comprising heterobifunctional
linker molecules, allowing photoresponsive host–guest com-
plexation with vesicles of amphiphilic a-CD and electrostatic
binding of the biomolecules. The crucial role of multivalency
for substrate binding was verified in comparative studies with
different linkers and target molecules. We utilized a modular
strategy for the controlled binding and release of four types of
DNA and six different proteins, demonstrating the large scope
of possible targets based on the same supramolecular plat-
form. The proof of concept, which we thereby established, can
potentially be adapted for the capture and release of RNA or
other biomolecules with multiple charges and ultimately to
a large number of structurally diverse targets such as charged
macromolecules or nanoparticles.
Absorption spectra and optical density at 600 nm (OD600) were
recorded on an Uvikon 923 (Konton Instruments) double-beam
spectrometer or V650 Spectrophotometer (JASCO). Samples
were prepared in 1.5 mL disposable PMMA cuvettes by using
HEPES buffer (20 mm HEPES, 10 mm EDTA, pH 7.2) as a solvent.
The optical density of 1 mL solution of amphiphilic a-cyclodex-
trin 1 was monitored, collecting data points every 12 s. Linker
molecules 2–5 were added as a 2 mm solution in milli-Q water
after 2 min. The corresponding protein or DNA was added at
4 min as a concentrated solution (60 mm–1 mm) in HEPES
buffer and the measurement was continued until the OD600
was constant.
Dynamic light scattering and zeta-potential measurements
DLS and zeta-potential measurements were performed on
a Nano ZS Zetasizer (Malvern Instruments Ltd.) at 298 K. Size
determination was conducted in 1.5 mL disposable PMMA cuv-
ettes, zeta potential was measured in disposable capillary cells
(DTS 1060, Malvern Instruments Ltd.) at 258C by using 1 mL of
amphiphilic a-cyclodextrin solution. Data was taken 60 min
after the addition of guest to host vesicles and immediately
after UV (350 nm) irradiations.
Experimental Section
Materials and synthesis
a-Cyclodextrin was kindly donated by Wacker Chemie (Burghau-
sen, Germany) and used without further purification. Double-
stranded DNA from salmon testes Type III (M 1.3·106 gmolÀ1, ca.
2000 bp) was purchased from Sigma–Aldrich (Taufkirchen, Germa-
ny). Single-stranded DNA (M50-mer 15427 gmolÀ1) was purchased
from Eurofins MWG Operon (Ebersberg, Germany). All other chemi-
cals were purchased from Sigma–Aldrich (Taufkirchen, Germany) or
Acros Organics (Schwerte, Germany) and used as received. Aque-
ous solutions were prepared with milli-Q water and organic sol-
vents were dried according to standard methods before use. The
synthesis and characterization of linker molecules 2--5 is described
in the Supporting Information. Analytical data for these molecules
are in agreement with their molecular structure, and NMR spectra
are provided as Supporting Information. The synthesis of amphi-
philic a-CD 1 was carried out as described previously.[12b]
Irradiation experiments
For the photoisomerization of azobenzene from trans to cis,
a Rayonet photochemical reactor (The Southern New England
Ultraviolet Company) with 16 RPR-3500 UV lamps emitting at
l=350 nm was used. The samples were irradiated in 5 to
10 steps of increasing exposure time up to a total of 25 to
40 min.
Acknowledgements
Preparation of vesicles
A stock solution of 1 in chloroform (2 mgmLÀ1) was prepared
and stored in the freezer. In a round bottom flask, an aliquot
of this solution was dried by slow rotary evaporation followed
by high vacuum, yielding a thin film of amphiphiles. Aqueous
buffer (20 mm HEPES, 10 mm EDTA, pH 7.2) was added and
stirred overnight. Unilamellar bilayer vesicles (CDV) were fabri-
cated by pressing the suspension through a polycarbonate
membrane (100 nm pore size) with a Liposofast manual
extruder.
We are grateful to the Graduate School of Chemistry for fellow-
ships to S.K.M.N. and A.S.
Keywords: cyclodextrins · host–guest systems · molecular
recognition · self-assembly · vesicles
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Published online on && &&, 0000
Chem. Eur. J. 2015, 21, 1 – 8
www.chemeurj.org
7
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
FULL PAPER
Cyclodextrin vesicles bind charged bio-
molecules, such as DNA or proteins, in
the presence of light-responsive
charged guest molecules. The com-
plexes can be disassembled under UV-
light irradiation based on trans/cis iso-
merization of the azobenzene guests
(see figure).
&
Self-Assembly
J. Moratz, A. Samanta, J. Voskuhl,
S. K. Mohan Nalluri, B. J. Ravoo*
&& – &&
Light-Triggered Capture and Release
of DNA and Proteins by Host–Guest
Binding and Electrostatic Interaction
&
&
Chem. Eur. J. 2015, 21, 1 – 8
www.chemeurj.org
8
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!