Sequence Programming with Dynamic Boronic Acid/Catechol Binary Codes

Article abstract of DOI:10.1021/jacs.9b03107

The development of a synthetic code that enables a sequence programmable feature like DNA represents a key aspect toward intelligent molecular systems. We developed herein the well-known dynamic covalent interaction between boronic acids (BAs) and catechols (CAs) into synthetic nucleobase analogs. Along a defined peptide backbone, BA or CA residues are arranged to enable sequence recognition to their complementary strand. Dynamic strand displacement and errors were elucidated thermodynamically to show that sequences are able to specifically select their partners. Unlike DNA, the pH dependency of BA/CA binding enables the dehybridization of complementary strands at pH 5.0. In addition, we demonstrate the sequence recognition at the macromolecular level by conjugating the cytochrome c protein to a complementary polyethylene glycol chain in a site-directed fashion.

Full text of DOI:10.1021/jacs.9b03107

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Communication
Sequence Programming with Dynamic Boronic Acid/Catechol Binary Codes
Marco Hebel, Andreas Riegger, Maksymilian Marek Zegota, Gönül Kizilsavas,
Jasmina Ga#anin, Michaela Pieszka, Thorsten Lückerath, Jaime A. S. Coelho,
Manfred Wagner, Pedro Miguel Pimenta Gois, David Y. W. Ng, and Tanja Weil
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b03107 • Publication Date (Web): 22 Aug 2019
Downloaded from pubs.acs.org on August 22, 2019
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Sequence Programming with Dynamic Boronic Acid/Catechol Bi-
nary Codes
Marco Hebel,1,2 Andreas Riegger,2 Maksymilian M. Zegota,1,2 Gönül Kizilsavas,1 Jasmina Gačanin,1,2
Michaela Pieszka,1,2 Thorsten Lückerath,1,2 Jaime A. S. Coelho,3 Manfred Wagner,1 Pedro M. P. Gois,3
David Y. W. Ng,1,* and Tanja Weil1,2,*
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1Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany
2Institute of Inorganic Chemistry I, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany
3Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
Supporting Information Placeholder
fulfils these criteria well.22 The binding complex is equipped with
ABSTRACT: The development of a synthetic code that enables a
1) small spatial requirement, 2) fast binding kinetics and 3) pH-
responsiveness within the physiological range (5.0 – 7.4).23 Hence,
its dynamic covalent binding capabilities have been applied
broadly in therapeutics,24 biosensors,25,26 stimulus responsive liga-
tion tools27 and as self-regenerative materials.28,29 Herein, we pro-
pose that BA/CA motifs in a binary sequence would encode molec-
ular recognition in a stimulus responsive fashion.
sequence programmable feature like DNA represents a key aspect
toward intelligent molecular systems. We developed herein the
well-known dynamic covalent interaction between boronic acids
(BA) and catechols (CA) into synthetic nucleobase analogs. Along
a defined peptide backbone, BA or CA residues are arranged to en-
able sequence recognition to their complementary strand. Dynamic
strand displacement and errors were elucidated thermodynamically
to show that sequences are able to specifically select their partners.
Unlike DNA, the pH dependency of BA/CA binding enables the
de-hybridization of complementary strands at pH 5.0. In addition,
we demonstrate the sequence recognition at the macromolecular
level by conjugating the cytochrome c protein to a complementary
polyethylene glycol chain in a site-directed fashion.
Molecular interactions in Nature are often involved in a complex
network of energy landscapes where individual components, from
small molecules to organelles, form transient systems on demand.1
Proteins have their origin within the genome – where molecular in-
formation is encoded and translated based on precise complexation
and spatially-controlled chemistry. In this respect, there has been
much progress in the creation of artificial DNA prototypes to pro-
gram molecular functions,2,3 adapting both supramolecular4-8 and
dynamic covalent interactions.9-12 Despite these successes in pur-
suit of artificial life, the advent of synthetic chemistry in this field
remains far slower than their biochemistry counterparts.13-16
The development of synthetic DNA-type systems is deceptively
challenging. On the sequence level, it is necessary that the interact-
ing motifs are small so that both sterical demand and synthesis are
not compromised by increasing sequence length. Molecularly, the
binding event should be selective for complementary sequences
while remaining dynamic and exchangeable in mild aqueous con-
ditions. At first glance, synthetic functional groups in supramolec-
ular chemistry (e.g. cyclodextrin,17 curcubituril,18 ureido-pyrimidi-
nones19) or dynamic covalent chemistry (e.g. spiropyran,20 dia-
rylethenes21) seem to satisfy the above criteria. However, most mo-
tifs are either sterically bulky, offer too high binding constants al-
ready for the first binding event and/or they are laborious to be in-
corporated along a sequence.
Figure 1. a) Peptide scaffold to code a binary BA/CA pairing. b)
Thermodynamic processes involved in multivalent effects, comple-
mentary and mismatched sequences.
The permutation between binary “1/0” events and the length of the
backbone defines the coding space. Inspired by peptide nucleic ac-
ids, a peptide backbone was designed to ensure greater hydrolytic
stability.30 Moreover, existing peptide synthesis methodologies fa-
cilitate the preparation of longer sequences, installation of custom-
izable end groups and flexibility of spacer groups i.e. lysine or ala-
nine to control solubility, steric demand or surface
Unlike most recognition motifs, the interaction between boronic
acids (BA) and electron rich vicinal diols such as catechols (CA)
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Scheme 1. Synthesis of BA containing amino acid 7 and the chemical structures of a small library of BA/CA peptide codes.
charges. As a demonstration in a broader context, a protein (cyto-
chrome c) and a polymer (polyethylene glycol) were conjugated via
these dynamic covalent tags to demonstrate recognition specificity
at the macromolecular level.
In each series, fluorescein labelled BA peptides act as the tem-
plate strand and are titrated with their complementary CA peptides.
For a single BA/CA binding event, (AX)1-(BX)1, a binding affinity
of 1,300 ± 300 M-1 was observed, which is consistent with pub-
lished data.32 By increasing the binding event to divalent (AX)2-
(BX)2 and trivalent (AX)3-(BX)3, a respective 10-fold (12,500 ±
1,100 M-1) and 70-fold (81,400 ± 7,300 M-1) increase were ob-
served. Importantly, the absence of binding errors to form unstruc-
tured aggregates was supported by the defined fluorescence decay
and dynamic light scattering (Figure S4). The binding of (AX)3-
(BX)3 was also confirmed independently by FRET (Figure S5). The
lesser increase in binding affinity with each subsequent binding
code suggests that energy is required to compensate the backbone
structure in the bound state. By bringing the findings into perspec-
tive of DNA hybridization, the binding affinity of (AX)3-(BX)3 is
comparable to about eight base pairs (with 50% G-C content) on a
DNA level.33,34
The unnatural amino acid 7 containing the BA was synthesized
based on a protocol for iodo-phenylalanine (Scheme 1).31 L-phenyl-
alanine was iodinated to afford 1, with the carboxylic acid and the
amine groups protected by the methyl ester (2) and the boc group
(3), respectively. Suzuki-Miyaura borylation was conducted to in-
stall the BA pinacol ester moiety (4) with a subsequent global
deprotection to yield the boronated L-phenylalanine 5. Here, a
switch in protecting groups is necessary because the pinacol ester
is sensitive to microwave conditions. Additionally, longer se-
quences containing multiple BA cause aggregation on the solid
phase. Thus, after the installation of the fmoc moiety (6), the BA
was protected with a highly bulky pinanediol to afford 7. The cor-
responding CA containing amino acid, dihydroxy-L-phenylalanine,
was commercially available.
The binding structure of the (AX)3-(BX)3 complex was character-
1
ized by multidimensional H NMR spectroscopy. The binding of
Peptide sequences containing all permutations of BA and CA in
a hexa/octa-peptide format were synthesized to elucidate the influ-
ence of sequence, length and positional defects. The amino acids
that do not participate in the coding segment are filled by lysines
(X) to improve water solubility. To demonstrate the chemical ver-
satility, the N-terminus was modified with reactive functionalities
i.e. amine, thiol or maleimide (Scheme 1). In this way, oligopep-
tides containing one, two and three BA [(AX)1, (AX)2, (AX)3] as
well as their complementary CA counterparts [(BX)1, (BX)2,
(BX)3] were synthesized. The binding affinities of the dynamic co-
valent interactions between (AX)1-(BX)1, (AX)2-(BX)2, (AX)3-
(BX)3 were evaluated by fluorescence microscale thermophoresis
in 300 mM phosphate buffer, pH 7.4 (Figure 2a).
the boronic acids and catechols leads to the complete transfor-
1
mation of the chemical environment, shifting the H aromatic sig-
nals of the components (Figure 2b, S6). Resonance peaks of the
boronic acids 1HAR in the total correlation spectroscopy (TOCSY)
were shifted into high-field confirming that the boron center be-
comes less electron withdrawing upon binding (Figure S7-8). Nu-
clear Overhauser effect spectroscopy (NOESY) analysis of (AX)3-
(BX)3 shows many additional and shifted intramolecular through
1
space H-couplings compared to the separate components (Figure
2c, S9-10). These new interactions ascertain the formation of chem-
ical environments that increase the intramolecular through
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Figure 2. Characterization of multivalent binding of complementary BA/CA codes. a) Binding affinity determination of (AX)1-(BX)1 (mon-
ovalent, blue), (AX)2-(BX)2 (divalent, red) and (AX)3-(BX)3 (trivalent, black) by fluorescence microscale thermophoresis in 300 mM phos-
phate buffer, pH 7.4. b) 1H NMR and c) 1H nuclear Overhauser effect spectroscopy (NOESY) of (AX)3, (BX)3 and (AX)3-(BX)3 complex in
300 mM phosphate buffer, pH 7.4, 9:1 (H2O:D2O), 298 K. d) 1H diffusion ordered spectroscopy (DOSY) of the (AX)3-(BX)3 complex against
(BX)3 in 300 mM phosphate buffer, pH 7.4, 9:1 (H2O:D2O), 298 K. e) MALDI-TOF of (AX)3-(BX)3 at pH 7.4 (top) and pH 5.0 (bottom). f)
Circular dichroism spectroscopy of (AX)3-(BX)3 and their separate components at phosphate buffer pH 7.4, 298 K.
space interactions between the aromatic groups and the Hα, Hβ of
the boronic acid or catechols. Diffusion ordered NMR (DOSY)
confirms the binding event as an increase in the diffusion time of
the complex (Figure 2d, S11). Additionally, the monovalent com-
plexes are stable to heat up to 70°C at the using variable tempera-
ture NMR (Figure S15-S19).
interaction between the complementary sequences (Figure S21).
Here, DFT calculations using a simplified structure revealed a low
activation energy (10 kcal mol-1) for the first boron-oxygen (cate-
chol) bond breaking step, representing the fast hydrolysis of the tet-
rahedral boron observed at acidic pH (Figure S26).
Interestingly, sequences containing consecutive BA/CA residues
without the alternating spacers (A3X3, B3X3) do not bind to their
complementary partners ≤500 µM (Table 1, Figure S22, S27).
Above this concentration, precipitation of A3X3 occurs, indicating
the importance of the lysine spacer in the alternating (AX) arrange-
ment providing both solubility and relief of steric constraints for
the binding event.
The observed BA-CA interaction was supported independently by
MALDI-TOF MS, where the formation of (AX)3-(BX)3 was char-
acterized by an m/z value at 2079.01 at pH 7.4 (Figure 2e, top).
Noteworthy, significant fragmentation of the complex occurs due
to the acidic nature of the matrix (α-cyano-4-hydroxycinnamic
acid, α-CHCA). At pH 5.0, only separate components of (AX)3 and
(BX)3 were found (Figure 2e, bottom). In the FTIR of (AX)3-(BX)3,
the vibrational mode at 1289 cm-1 was lost while a new peak was
observed at 1495 cm-1 suggesting an increase in bond energy and
C=C character for the dynamic covalent interaction (Figure
S20).35,36 The electron deficient boron withdraws electrons through
the vicinal diols, which reduces the electron density of the catechol
aromatic system.
Next, we encoded a sequence specific binding event by using (1)
mixed sequences (ABA and BAB) and (2) inclusion of a non-bind-
ing event Y. Importantly, mixed sequences contain partially com-
plementary parts, whereas the non-binding event provides an “er-
ror” in the sequence. We observed that the ABA-BAB interacts
with a binding affinity of 79,400 ± 5,200 M-1, which is comparable
to the homogenous (AX)3-(BX)3 pairs (Table 1). However, the in-
teraction took significantly longer (about 8 h) suggesting that error
correction requires a certain timeframe, similar to DNA.37,38 On the
other hand, sequence hybridization can be weakened correspond-
ingly by AAYA-BYBB, where Y is a non-binding, non-interacting
amino acid (alanine). The increase in the chain length also increases
the energy needed to compensate, resulting in a lower binding af-
finity (21,100 ± 6,100 M-1) to a divalent level. Mismatched partners
such as (AX)3-BYBB further weakens complementarity. Taking
another mismatch pair of identical length, BAB-(BX)3, non-bind-
ing residues appear 1H NMR (Figure S12) indicating very weak in-
teractions.
Circular dichroism spectroscopy found that, at pH 7.4, the
(AX)3-(BX)3 complex shows a strong negative molar ellipticity at
210 nm, corresponding to the n-π* transition of the carbonyl group
(Figure 2f, S21). Together with the absence of Cotton effects, these
observations imply that the tetrahedral boron center has a strong
through-space effect on the C=O bond. Density functional theory
(DFT) calculations confirmed that hydrogen bonding interactions
between the hydroxyl groups of the tetrahedral boron and the car-
boxyl groups of lysines contribute to lowering the electronic energy
of (AX)3-(BX)3 (Figure 3a, S23-24). The combination of these ob-
servations seems to corroborate the shifts associated with the
TOCSY, NOESY cross-peaks. In contrast, at pH 5.0, there is no
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Figure 3. a) Model of the DFT optimized structure of (AX)3-(BX)3 at (B3LYP/6-31G(d) theory level (see Supporting Information). b)
Displacement reaction on a fluorescein-(AX)3 template: Monovalent (BX)1 was titrated to achieve maximum binding (fluorescence, blue)
followed by the addition of increasing amounts of Dylight650-(BX)3 to displace (BX)1 (FRET, black). c) Sequence dependent discrimination
between complementary AAYA-BYBB and mismatching (AX)3-BYBB peptide based on titration. d) Quantification of binding of PEG5000
-
(AX)3 with CytC-(BX)3 at 100 µM using Alizarin Red S assay. e) Characterization of the recognition by CytC-(BX)3 (13,886 g mol-1) with
PEG5000-(AX)3 (6,468 g mol-1) yielding PEG5000-(AX)3(BX)3-CytC (calcd. MW: 20,036 g mol-1, detected MW 20,243 g mol-1, matrix
CHCA) using MALDI-TOF MS.
sensor, Alizarin Red S in a titration assay (Figure 3d). The construct
was characterized additionally with MALDI-TOF MS albeit with
partial dissociation of the construct due to the acidic matrix (Figure
3e). Additionally, topological height increases due to complexation
was visualized by atomic force microscopy (Figure S19).43
Table 1. Summary of association constants of different
matching/mismatching sequences
In summary, we have demonstrated, to the best of our
knowledge, the first application of boronic acid chemistry in mo-
lecular sequence programming under physiological conditions. By
combining the recognition and binding customization of boronic
acid/catechol chemistry with a peptide scaffold, synthetic binary
codes were created, in which binding and dynamic displacement
was directed in a predictable and logical manner. In addition, the
pH responsiveness of the chemistry adds an extra trigger to control
the hybridization process. Assisted by the burgeoning field of site-
selective protein chemistry,44 the application of complementary se-
quences to the protein cytochrome c and PEG5000 further underlines
the potential to create defined and dynamic macromolecular assem-
blies. We envision that the technology provides a synthetic plat-
form for programming macromolecular architectures to possess
complex dynamic features.
Since strand displacement dynamics is an important tool in DNA
nanotechnology,38-40 we investigate the displacement dynamics of
our conjugate by the binding of monovalent (BX)1 and a trivalent
(BX)3 against a (AX)3 template. The fluorescein-(AX)3 was first ti-
trated with (BX)1 until binding saturation (Figure 3b, black). Dis-
placement and sorting was then achieved by titrating the (AX)3-
(BX)1 against Dylight650-(BX)3, monitored independently by
FRET. The intersection between the measurements indicates a stoi-
chiometric ratio where (BX)1 and (BX)3 can competitively displace
each other by at least 50% (Figure 3b). For (BX)1 to displace (BX)3
by 50%, a stoichiometric factor of >4000 mol% is required. On the
other hand, (BX)3 would only require >2.5 mol% due to its multi-
valent effect.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website. Materials and methods, characterization tech-
niques and instrumentation as well as supporting figures are pro-
vided in the supporting information.
Based on these findings, the established binary codes could be
used to enable recognition of macromolecules i.e. proteins and pol-
ymers. As PEGylation of proteins remain an important aspect in
protein therapeutics,41,42 we functionalized PEG5000 and yeast cyto-
chrome c (CytC) with (AX)3 and (BX)3 respectively. The conver-
sion to PEG5000-(AX)3(BX)3-CytC was quantified by a fluorogenic
AUTHOR INFORMATION
Corresponding Author
david.ng@mpip-mainz.mpg.de, weil@mpip-mainz.mpg.de
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Brooks, W. L. A.; Sumerlin, B. S. Synthesis and Applications of
Notes
Boronic Acid-Containing Polymers: From Materials to Medicine. Chem.
Rev. 2016, 116, 1375-1397.
1
The authors declare no competing financial interests.
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Akgun, B.; Hall, D. G. Boronic Acids as Bioorthogonal Probes
ACKNOWLEDGMENT
for Site-Selective Labeling of Proteins. Angew. Chem. Int. Ed. 2018, 57,
13028-13044.
(24)
Veiros, L. F.; Florindo, H. F.; Gois, P. M. P. Modular Assembly of
Reversible Multivalent Cancer-Cell-Targeting Drug Conjugates. Angew.
Chem. Int. Ed. 2017, 56, 9346-9350.
The project was funded by the Deutsche Forschungsgemeinschaft
(DFG, German Research Foundation) – Project number 316249678
– SFB 1279 (C01) and Project number: 318290668 – SPP 1923 as
well as by an ERC Synergy Grant under grant agreement No.
319130 (BioQ). M. M. Zegota thanks the Marie Curie International
Training Network Protein Conjugates for a research scholarship.
Santos, F. M. F.; Matos, A. I.; Ventura, A. E.; Gonçalves, J.;
(25)
Wu, X.; Li, Z.; Chen, X.-X.; Fossey, J. S.; James, T. D.; Jiang,
Y.-B. Selective sensing of saccharides using simple boronic acids and their
aggregates. Chem. Soc. Rev. 2013, 42, 8032-8048.
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Sun, X.; James, T. D.; Anslyn, E. V. Arresting “Loose Bolt”
REFERENCES
Internal Conversion from −B(OH)2 Groups is the Mechanism for Emission
Turn-On in ortho-Aminomethylphenylboronic Acid-Based Saccharide
Sensors. J. Am. Chem. Soc. 2018, 140, 2348-2354.
(1)
inspired systems. Nat. Nanotechnol. 2016, 11, 585-592.
(2) Hirao, I.; Kimoto, M.; Yamashige, R. Natural versus Artificial
Grzybowski, B. A.; Huck, W. T. S. The nanotechnology of life-
(27)
Seidler, C.; Zegota, M. M.; Raabe, M.; Kuan, S. L.; Ng, D. Y.
Creation of Base Pairs in DNA: Origin of Nucleobases from the
Perspectives of Unnatural Base Pair Studies. Acc. Chem. Res. 2012, 45,
2055-2065.
W.; Weil, T. Dynamic Core–Shell Bioconjugates for Targeted Protein
Delivery and Release. Chem. Asian J. 2018, 13, 3474-3479.
(28)
dynamic boronic acid chemistry. Tetrahedron 2017, 73, 4979-4987.
(29) Smithmyer, M. E.; Deng, C. C.; Cassel, S. E.; LeValley, P. J.;
Sumerlin, B. S.; Kloxin, A. M. Self-Healing Boronic Acid-Based Hydrogels
for 3D Co-cultures. ACS Macro Lett. 2018, 7, 1105-1110.
(30)
chimeras: from high binding affinity towards biological function. Biol.
Chem. 1998, 379, 1045-1052.
(31)
Lee, J. Efficient Synthesis of a Phosphinate Bis-Amino Acid and Its Use in
the Construction of Amphiphilic Peptides. J. Org. Chem. 1994, 59, 4206-
4210.
Seidler, C.; Ng, D. Y. W.; Weil, T. Native protein hydrogels by
(3)
Liu, Y.; Lehn, J.-M.; Hirsch, A. K. H. Molecular Biodynamers:
Dynamic Covalent Analogues of Biopolymers. Acc. Chem. Res. 2017, 50,
376-386.
(4)
Swain, J. A.; Iadevaia, G.; Hunter, C. A. H-Bonded Duplexes
based on a Phenylacetylene Backbone. J. Am. Chem. Soc. 2018, 140,
11526-11536.
Uhlmann, E. Peptide nucleic acids (PNA) and PNA-DNA
(5)
Stross, A. E.; Iadevaia, G.; Núñez-Villanueva, D.; Hunter, C. A.
Sequence-Selective Formation of Synthetic H-Bonded Duplexes. J. Am.
Chem. Soc. 2017, 139, 12655-12663.
Lei, H.; Stoakes, M. S.; Schwabacher, A. W.; Herath, K. P. B.;
(6)
Stabilities. Acc. Chem. Res. 2012, 45, 2077-2087.
(7) Zhang, Y.; Cao, R.; Shen, J.; Detchou, C. S. F.; Zhong, Y.;
Gong, B. Molecular Duplexes with Encoded Sequences and
(32)
Martínez-Aguirre, M. A.; Villamil-Ramos, R.; Guerrero-
Wang, H.; Zou, S.; Huang, Q.; Lian, C.; Wang, Q.; Zhu, J.; Gong, B.
Hydrogen-Bonded Duplexes with Lengthened Linkers. Org. Lett. 2018, 20,
1555-1558.
Alvarez, J. A.; Yatsimirsky, A. K. Substituent Effects and pH Profiles for
Stability Constants of Arylboronic Acid Diol Esters. J. Org. Chem. 2013,
78, 4674-4684.
(33)
calculator. Nucleic Acid. Res. 2007, 35, W43-W46.
(34) Ratilainen, T.; Holmén, A.; Tuite, E.; Haaima, G.; Christensen,
L.; Nielsen, P. E.; Nordén, B. Hybridization of Peptide Nucleic Acid.
Biochemistry 1998, 37, 12331-12342.
(35)
O-H Bond Dissociation Enthalpies and Ionization Potentials of Catechols:
A DFT Study and Its Implications in the Rational Design of Phenolic
Antioxidants and Elucidation of Structure–Activity Relationships for
Flavonoid Antioxidants. Chem. Eur. J. 2003, 9, 502-508.
(8)
Makiguchi, W.; Tanabe, J.; Yamada, H.; Iida, H.; Taura, D.;
Kibbe, W. A. OligoCalc: an online oligonucleotide properties
Ousaka, N.; Yashima, E. Chirality- and sequence-selective successive self-
sorting via specific homo- and complementary-duplex formations. Nat.
Commun. 2015, 6, 7236.
(9)
Iida, H.; Ohmura, K.; Noda, R.; Iwahana, S.; Katagiri, H.;
Ousaka, N.; Hayashi, T.; Hijikata, Y.; Irle, S.; Yashima, E. Double-
Stranded Helical Oligomers Covalently Bridged by Rotary Cyclic Boronate
Esters. Chem. Asian J. 2017, 12, 927-935.
Zhang, H.-Y.; Sun, Y.-M.; Wang, X.-L. Substituent Effects on
(10)
Yashima, E.; Ousaka, N.; Taura, D.; Shimomura, K.; Ikai, T.;
Maeda, K. Supramolecular Helical Systems: Helical Assemblies of Small
Molecules, Foldamers, and Polymers with Chiral Amplification and Their
Functions. Chem. Rev. 2016, 116, 13752-13990.
(36)
Gulley-Stahl, H.; Hogan, P. A.; Schmidt, W. L.; Wall, S. J.;
Buhrlage, A.; Bullen, H. A. Surface Complexation of Catechol to Metal
Oxides: An ATR-FTIR, Adsorption, and Dissolution Study. Environ. Sci.
Technol. 2010, 44, 4116-4121.
(11)
Sisco, S. W.; Moore, J. S. Homochiral Self-Sorting of BINOL
Macrocycles. Chem. Sci. 2014, 5, 81-85.
(12)
Epstein, E. S.; Martinetti, L.; Kollarigowda, R. H.; Carey-De La
(37)
Zhang, J. X.; Fang, J. Z.; Duan, W.; Wu, L. R.; Zhang, A. W.;
Torre, O.; Moore, J. S.; Ewoldt, R. H.; Braun, P. V. Modulating
Noncovalent Cross-links with Molecular Switches. J. Am. Chem. Soc. 2019,
141, 3597-3604.
Dalchau, N.; Yordanov, B.; Petersen, R.; Phillips, A.; Zhang, D. Y.
Predicting DNA hybridization kinetics from sequence. Nat. Chem. 2017,
10, 91-98.
(13)
Powell, K. How biologists are creating life-like cells from
(38)
Platnich, C. M.; Hariri, A. A.; Rahbani, J. F.; Gordon, J. B.;
scratch. Nature 2018, 563, 172-175.
Sleiman, H. F.; Cosa, G. Kinetics of Strand Displacement and Hybridization
on Wireframe DNA Nanostructures: Dissecting the Roles of Size,
Morphology, and Rigidity. ACS Nano 2018, 12, 12836-12846.
(39)
controllers for directing material expansion. Nat. Commun. 2018, 9, 3766.
(40) Machinek, R. R. F.; Ouldridge, T. E.; Haley, N. E. C.; Bath, J.;
Turberfield, A. J. Programmable energy landscapes for kinetic control of
DNA strand displacement. Nat. Commun. 2014, 5, 5324.
(41)
Crowley, P. B. Noncovalent PEGylation via Sulfonatocalix[4]arene–A
Crystallographic Proof. Bioconjugate Chem. 2018, 29, 3999-4003.
(42)
Proteins: Recent Developments. J. Org. Chem. 2014, 79, 10727-10733.
(43) Takeda, K.; Uchihashi, T.; Watanabe, H.; Ishida, T.; Igarashi,
K.; Nakamura, N.; Ohno, H. Real-time dynamic adsorption processes of
cytochrome c on an electrode observed through electrochemical high-speed
atomic force microscopy. PLOS One 2015, 10, e0116685-e0116685.
(14)
Göpfrich, K.; Platzman, I.; Spatz, J. P. Mastering Complexity:
Towards Bottom-up Construction of Multifunctional Eukaryotic Synthetic
Cells. Trends Biotechnol. 2018, 36, 938-951.
Fern, J.; Schulman, R. Modular DNA strand-displacement
(15)
applications. Mater. Today 2016, 19, 516-532.
(16) Seeman, N. C.; Sleiman, H. F. DNA nanotechnology. Nat. Rev.
Mater. 2017, 3, 17068.
Xu, C.; Hu, S.; Chen, X. Artificial cells: from basic science to
(17)
Crini, G. Review: A History of Cyclodextrins. Chem. Rev. 2014,
Mummidivarapu, V. V. S.; Rennie, M. L.; Doolan, A. M.;
114, 10940-10975.
(18)
Barrow, S. J.; Kasera, S.; Rowland, M. J.; del Barrio, J.;
Scherman, O. A. Cucurbituril-Based Molecular Recognition. Chem. Rev.
2015, 115, 12320-12406.
Nischan, N.; Hackenberger, C. P. R. Site-specific PEGylation of
(19)
Supramolecular biomaterials. Nat. Mater. 2015, 15, 13-26.
(20) Klajn, R. Spiropyran-based dynamic materials. Chem. Soc. Rev.
2014, 43, 148-184.
Webber, M. J.; Appel, E. A.; Meijer, E. W.; Langer, R.
(21)
Kathan, M.; Eisenreich, F.; Jurissek, C.; Dallmann, A.; Gurke,
(44)
Krall, N.; da Cruz, F. P.; Boutureira, O.; Bernardes, G. J. L. Site-
J.; Hecht, S. Light-driven molecular trap enables bidirectional manipulation
of dynamic covalent systems. Nat. Chem. 2018, 10, 1031-1036.
selective protein-modification chemistry for basic biology and drug
development. Nat. Chem. 2015, 8, 103-113.
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