Selective modification of a native protein in a patient tissue homogenate using palladium nanoparticles

Article abstract of DOI:10.1039/c9cc07803g

We have developed new benign palladium nanoparticles able to catalyze the Suzuki-Miyaura cross-coupling reaction on human thyroglobulin (Tg), a naturally iodinated protein produced by the thyroid gland, in homogenates from patients' tissues. This represents the first example of a chemoselective native protein modification using transition metal nanoobjects in near-organ medium.

Full text of DOI:10.1039/c9cc07803g

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Selective modification of a native protein in a
patient tissue homogenate using palladium
nanoparticles†
Cite this: Chem. Commun., 2019,
5, 15121
5
Received 4th October 2019,
Accepted 18th November 2019
a
a
b
b
Arnaud Peramo, Anaelle Dumas, Hynd Remita,
Mireille Benoıt,
ˆ
¨
c
d
d
d
Stephanie Yen-Nicolay, Raphael Corre, Ruy A. Louzada, Corinne Dupuy,
Shannon Pecnard, Benoit Lambert, Jacques Young, Didier Desmaele
Patrick Couvreur
¨
DOI: 10.1039/c9cc07803g
a
e
e
a
and
¨
a
*
rsc.li/chemcomm
We have developed new benign palladium nanoparticles able to catalyze strained alkynes were developed but they showed specificity
7
the Suzuki–Miyaura cross-coupling reaction on human thyroglobulin problems. Many other approaches were proposed including
8
9
(
Tg), a naturally iodinated protein produced by the thyroid gland, in Staudinger ligation, hydrazine and oxime ligation and more
1
0
homogenates from patients’ tissues. This represents the first example recently the inverse-electron demand Diels–Alder reactions
of a chemoselective native protein modification using transition between tetrazines and trans-cyclooctenes or vinylboronic
1
1
1
2
metal nanoobjects in near-organ medium.
acid. Transition metal-mediated reactions that involve reactive
chemical groups not found in natural systems provide also
The selective functionalization of proteins with a chemical fascinating possibilities for the selective in vivo chemical manipula-
13,14
15,16
17
reporter inside complex biological media has been the subject tion of proteins.
Gold
and ruthenium have been used for
of intensive studies during the last decade for investigating the the selective uncaging of fluorescent probes but, palladium
1
,2
dynamics and function of biomolecules.
This approach appeared as one of the most promising metals, giving rise to
usually involves the genetic or metabolic incorporation of a numerous applications in biology including in vivo prodrug
1
8–20
small organic reporter carrying a bio-orthogonal reactive group activation or intracellular labelling.
into a target protein within the cell. The modification of the Recently, site-specific protein derivatization by Suzuki–Miyaura
resulting tagged protein may then be achieved through a reaction of genetically encoded p-iodophenylalanine (pIPhe) was
selective reaction using an exogenous probe. The identification demonstrated using a water-soluble palladium catalyst both
2
1
22
of a selective reaction using a non-perturbing and cell permeable in vitro and in living bacterial cells. Nevertheless, the need
chemical handle that is inert towards other cellular components to use a high concentration of palladium, probably to surmount
and will react rapidly with its partners under physiological the non-specific sequestration of the metal by surrounding
3
conditions represents the main challenge of this approach. As biomolecules, could hamper further in vivo applications. This
a result, only few chemical reactions fulfilling all these criteria issue could be overcome to some extent by using nanoformula-
have been developed. Among them, the Cu-catalyzed alkyne– tions of palladium which were reported to allow cross-coupling
azide cycloaddition has become one of the most commonly used reactions in living mammalian cells, thanks to their ability to
4
,5
bioorthogonal conjugation reaction. However, the cytotoxicity cross the cell membrane, hence improving palladium cellular
6
23
of Cu ions has limited the use of this reaction in living systems.
uptake. Despite these influential advances, palladium nano-
As an alternative, copper-free versions of this ligation involving particles have never been used to modify a natural protein with
direct therapeutic potential. In this study, we provide the first
a
Institut Galien Paris-Sud, UMR 8612, CNRS Univ. Paris-Sud,
example of covalent modification of human thyroglobulin (Tg),
an iodinated native protein, involved in the pathogenesis and
the progression of the Graves’s disease or in the metastatic
papillary thyroid carcinoma. Indeed, using Suzuki–Miyaura
cross-coupling reaction catalyzed by palladium nanoparticles
(Pd NPs), we made the first proof of concept that a target native
protein may be chemically altered, directly in a patient tissue
homogenate. This brings the use of bioorthogonal reactions a
step ahead, closer to possible biomedical applications.
Universit ´e Paris-Saclay, Facult ´e de Pharmacie 5 rue Jean-Baptiste Cl ´e ment,
9
2290 Chatenay-Malabry, France. E-mail: patrick.couvreur@u-psud.fr
b
Laboratoire de Chimie Physique, UMR 8000-CNRS, B aˆ timent 349,
Universit ´e Paris-Sud, Universit ´e Paris-Saclay, Rue Michel Magat, 91400 Orsay,
9
1405 Orsay, France
c
Trans-Prot, UMS IPSIT, Univ. Paris-Sud, Universit ´e Paris-Saclay,
Facult ´e de Pharmacie 5 rue JB Cl ´e ment, 92296 Ch aˆ tenay-Malabry, France
Institut de Canc ´e rologie Gustave Roussy, UMR8200 CNRS,
d
1
14 rue Edouard Vaillant, 94805 Villejuif, France
e
H oˆ pital Bic ˆe tre, 78 rue du G ´e n ´e ral Leclerc, 94270 Le Kremlin-Bic ˆe tre, France
To harness the unique reactivity of palladium while preserving
its biocompatibility we first explored the reactivity of small
†
Electronic supplementary information (ESI) available: Full experimental and
spectroscopic data. See DOI: 10.1039/c9cc07803g
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Scheme 1 Suzuki–Miyaura coupling reactions catalyzed by Pd NPs with
iodinated amino acids in phosphate buffer.
Fig. 1 (A) TEM images of CPCl/Pd 1 : 1, (B) TEM images of PVP : Pd 1 : 100;
structure, TEM images suggested that they were constituted of
nanocrystalline Pd embedded in the polymer. Interestingly,
biological evaluation revealed very low cytotoxicity on both Raw
(C) cell viability of Pd NPs on Raw 264.7. (D) Cell viability of Pd NPs on primary
culture of human thyrocytes from patient tissue after 24 h incubation.
264.7 macrophages and primary culture of human thyrocytes
palladium nanoparticles entrapped into larger polymeric nano- directly arising from patient tissue (IC50 4 1 mM) (Table 1).
2
4
particles of poly(lactic-co-glycolic acid)–polyethyleneglycol,
a
Then, the catalytic activity of the two Pd nanoformulation was
25
material which demonstrated clinical safety. However, long-term evaluated on the Suzuki–Miyaura cross-coupling reaction of
stability concerns of this formulation compelled us to search for a N-Boc-4-iodo-phenylalanine or N-Boc-4-iodo-thyrosine in pH 8
more robust catalyst. We then investigated the palladium urchin- phosphate buffer using 1% of Pd Nano catalyst (Scheme 1). In
like nanostructures (Pd-Urchin NPs) developed by Ksar F. et al.,
assuming that their 3D porous morphology would offer a large triolborate potassium salts are better partners than boronic acids
surface area embedding high catalytic activity. The Pd-Urchin NPs for the C–C bond forming reaction catalyzed by Pd NPs. Phenyl
were obtained by slow reduction of (NH Cl Pd(H
O) in the cyclic triolborate potassium salt was thus selected as nucleophilic
presence of one equiv. of cetylpyridinium (CPCl) as a stabilizing species. Impressively, a full conversion was observed by H NMR
26
line with our previous findings, it was found that aryl cyclic
24
3
)
4
2
2
1
agent upon g-irradiation, a very efficient technique to synthesize after only 2 h incubation at 37 1C with all nanoformulations
27
nanoparticles of controlled size and shape (Fig. 1A). Although (Table 2 and Table S1, Fig. S2, ESI†).
palladium-containing NPs have previously shown satisfactory
Moreover, the reaction was also tested at pH 6 and pH 7 to
2
8
cellular compatibility, the presence of CPCl surfactant in make sure that the reaction was not limited to basic media and
the present nanostructure required careful examination. We, susceptible to proceed even under slightly acidic conditions such as
indeed, observed that this formulation was cytotoxic on human can be found in some subcellular compartments (i.e. late endosomes
primary thyroid cells isolated from histologically non-tumor and lysosomes). When the reaction was catalyzed by urchin-shape
tissue and on macrophage Raw 264.7 cell line with IC50
2
o
CPCl : Pd; 1 : 1 NPs at the lower pH, the conversion rate of the
0–50 mM after 24 h incubation time (Table 1 and Fig. 1C and D). starting material was affected, whereas no influence of the pH was
Attempts to decrease the toxicity by reducing the amount of CPCl detected when the cross-coupling was catalyzed by PVP–Pd NPs
either in the preparation steps or by post-synthetic dialysis were (Table 2 and Table S1, ESI†). According to these results, all further
fruitless (see ESI,† Fig. S1). Replacement of CPCl by another experiments were conducted with the PVP : Pd 1 : 100 catalyst. To
surfactant was therefore investigated. In this instance, we turned investigate the catalytic activity of the Pd NPs on a biological
our attention to the use of polyvinylpyrrolidone (PVP) as it was macromolecule, the direct arylation of the naturally iodinated bovine
reported to give stable Pd NPs upon reduction of Pd(II) salt by thyroglobulin (Tg) was tested (Scheme 2). This commercially
3
1
ultrasonic irradiation. Moreover, palladium-PVP stabilized NPs available 640 kD dimeric glycoprotein was found to possess
were found to catalyze Suzuki–Miyaura cross-coupling reactions thirty five iodinated tyrosine residues in the form of iodotyrosine
2
9,30
in water.
In the event, it was discovered that g-irradiation of
an aqueous solution of (NH ) Cl Pd(H O) in the presence of
3
4
2
2
Table 2 Suzuki–Miyaura cross-coupling reactions in water between
mol% of PVP provided highly stable nanosuspension of Pd NPs iodinated amino acids and phenyl boronic acid derivatives catalyzed by
1
with narrow size distribution around 70 nm (DLS). Transmission Pd NPs at different pH
electron microscopy (TEM) imaging showed nanobead-like struc-
tures with average particle size around 50 nm (Fig. 1B and Fig. S2,
a
No.
Catalyst
RI
Organoboron
pH
Conv. (%)
1
2
3
7
8
9
CPCl : Pd; 1 : 1
CPCl : Pd; 1 : 1
CPCl : Pd; 1 : 1
PVP : Pd; 1 : 100
PVP : Pd; 1 : 100
PVP : Pd; 1 : 100
1
2
2
1
1
1
3
3
4
4
4
4
8.0
8.0
8.0
8.0
7.0
6.0
48
70
90
98
98
98
ESI†). Although these objects no longer displayed the urchin-shape
Table 1 Size, surface charge (zeta potential) and cytotoxic activity of Pd NPs
Size
(nm)
z-Potential
(mV)
IC50 (mM)
(raw)
IC50 (mM)
(thyrocytes)
1
3
equiv. R-I, 3 equiv. R-B(OR) , 1 mol% Pd NPs, PBS, 37 1C, 2 h.
1
NPs
a
Conversions were determined by H NMR spectroscopy on the crude
CPCl:Pd;
PVP:Pd;
47.6
70.0
+19.7
+2.9
10
41000
48
41000
reaction mixture analyzing the C-3 methylene signal of the N-Boc
amino-acids (Fig. S2 and S3, ESI).
1
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Scheme 2 Suzuki–Miyaura cross-coupling reactions on iodinated Tg
catalyzed by Pd NPs.
0
(
mono- or diiodotyrosine) and iodothyronine (3,5,3 -triiodothyronine
Scheme 3 Synthetic route of the biotin cyclic triolborate probe.
0
0
or 3,5,3 ,5 -tetraiodothyronine) as evidenced by MS/MS analysis
after 1D SDS-PAGE separation and chymotrypsin digestion of the
Tg containing band (Fig. S4 and Table S2, ESI†).
3
2
but more notably established the absence of non-specific labeling
37,38
The detection of small chemical modifications within such a due to the eventual formation of protein–boronate adducts.
large protein involving heterogeneous post-translational iodination Having secured an easily detectable coupling partner capable to
represented therefore a major challenge. Proteomic analysis was modify Tg via Suzuki–Miyaura cross-coupling, we integrated the
first used to address a qualitative evaluation of the cross-coupling possibility to perform the bioorthogonal ligation in a complex
reaction with phenylboronate. The detection of specific modified biological mixture. In vivo, Tg is iodinated within the follicles in
39
tyrosines was achieved by mass spectrometry after Collision- thyroid gland at the thyrocyte surface. Noteworthy, simple 2D cell
33
Induced Dissociation (CID)-fragmentation using a LTQ-Orbitrap culture of thyrocytes provided only un-iodinated Tg not suitable for
followed by studies of the fragmentation pathways of protonated our study and, in addition, the expression of Tg rapidly declined
peptides providing inter alias C-terminal ammonium y ion series after few passage numbers. Commercially available FRTL and
and N-terminal b acylium ion series as previously reported by FRTL-5 cell lines derived from the thyroid gland of Fisher rats
3
4
Dedieu. The obtained fragments were identified by X!Tandem- were initially investigated to access iodinated Tg. However, it was
3
5
Pipeline (software version 0.2.24) by comparison with protein found that these cell lines either didn’t express Tg or produced
sequence P01267 from Uniprot database. A total of 17 tyrosines un-iodinated Tg (Table S3 and Fig. S11, ESI†). Therefore, in quest
modified with one or two phenyl residues were detected on the for a pertinent model for the cross-coupling reaction on a naturally
Tg (about 50% of the total iodinated tyrosines) after 24 h iodinated protein, it was decided to carry out this reaction into
incubation in the presence of PVP–Pd NPs and potassium phenyl tissue homogenates arising from thyroid biopsies obtained from
cyclic triolborate (Table S2 and Fig. S5, ESI†). This result thyroidectomy on Grave’s disease patients. Tg concentration in the
ꢁ
1
established the covalent C–C binding between the phenyl residue homogenate was estimated to be 7.4 ꢀ 0.4 mg mL by ELISA
and the native iodinated protein through Pd nanoobject. To further (ESI,† S8). Incubation of phenyl cyclic triolborate in the tissue
validate the ability of PVP–Pd NPs to achieve C–C bond formation homogenate in the presence of 1 mol% of PVP–Pd NPs followed by
with proteins and to avoid any non-specific reaction, an immuno- proteomic analysis of the extracted Tg indicated that iodinated
detection assay was set out. Because streptavidin conjugated to thyrosine residues were covalently modified (Table S4, ESI†). We
horse-radish peroxidase is commonly used as a standard for next tested the performance of the system to tag the human Tg with
immunoblotting protein detection, a biotinylated probe was the biotinylated probe. In the event, after 24 h incubation with
designed and synthesized. This probe was obtained by coupling PVP–Pd NPs and protein separation by SDS-PAGE gel, immuno-
a biotin head to a reactive aryl cyclic triolborate through an blotting analysis showed a bright fluorescent band at Tg molecular
ethylenedioxy linker, in order to allow detection with streptavidin. weight that provided evidence of the covalent coupling. The
Briefly, as depicted in Scheme 3, biotin was first conjugated to a absence of fluorescence in all the control experiments confirmed
0
short o,o -diaminotriethyleneglycol spacer to provide the the full chemoselectivity of the process (Fig. 2D and Fig. S12, ESI†).
3
6
known biotin amide derivative. Condensation of the latter
In summary, we have found that the Suzuki–Miyaura cross-
with 4-carboxyphenyl pinacol boronic ester and transesterifica- coupling reaction of aryl cyclic triolborate salts catalyzed by Pd
tion with 2-(hydroxymethyl)-2-methylpropane-1,3-diol in the NPs allowed a selective modification of a naturally iodinated
presence of KOH provided the required biotin cyclic triolborate protein in near intra-organ medium. Coupling was observed
probe. With the biotin probe in hand, the stage was set for with simple aromatic rings but also with a more complex
exploring the coupling reaction with the Tg.
biotinylated probe by Western-blotting.
After 24 h incubation of the bovine Tg with the biotinylated
Combined with the low cytotoxicity of the PVP–Pd NPs, this
probe in the presence of 50 equiv. of PVP–Pd NPs, immuno- new tool may provide a unique example of specific transition-
blotting analysis showed fluorescence around 300 kDa, corres- metal mediated reactions in a complex and natural biological
ponding to Tg, whereas nothing was detected in the control medium that does not require genetic modification. This opens
experiments without Pd NPs or without the biotinylated probe up the possibility to post-transcriptionally control the levels of
(Fig. S10, ESI†). This result confirmed the C–C bond formation thyroglobulin and thyroid hormones by attaching a tag able to
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9
1
D. K. K ¨o mel and E. T. Kool, Chem. Rev., 2017, 117, 10358–10376.
0 D. S. Liu, A. Tangpeerachaikul, R. Selvaraj, M. T. Taylor, J. M. Fox
and A. Y. Ting, J. Am. Chem. Soc., 2012, 134, 792.
11 J. W. Wollack, B. J. Monson, J. K. Dozier, J. J. Dalluge, K. Poss,
S. A. Hilderbrand and M. D. Distefano, Chem. Biol. Drug Des., 2014,
8
4, 140.
1
2 S. Eising, N. G. A. van der Linden, F. Kleinpenning and K. M.
Bonger, Bioconjugate Chem., 2018, 29, 982.
Fig. 2 (A) Separation of homogenate proteins by 1D-SDS Page gel (stain 13 Y. Gong and L. Pan, Tetrahedron Lett., 2015, 56, 2123.
1
1
4 J. M. Antos and M. B. Francis, Curr. Opin. Chem. Biol., 2006, 10, 253.
5 K. Tsubokura, K. K. H. Vong, A. R. Pradipta, A. Ogura, S. Urano, T. Tahara,
S. Nozaki, H. Onoe, Y. Nakao, R. Sibgatullina, A. Kurbangalieva,
Y. Watanabe and K. Tanaka, Angew. Chem., Int. Ed., 2017, 56, 3579.
6 A. M. P ´e rez-L ´o pez, B. Rubio-Ruiz, V. Sebasti ´a n, L. Hamilton, C. Adam,
T. L. Bray, S. Irusta, P. M. Brennan, G. C. Lloyd-Jones, D. Sieger,
J. Santamaria and A. Unciti-Broceta, Angew. Chem., Int. Ed., 2017,
free image), (B) stain free image after protein transfer, (C) detection of
Human Thyroglobulin on nitrocellulose membrane was probed with goat
anti-human thyroglobulin monoclonal antibody followed by horseradish
peroxidase (HRP)-conjugated anti-goat secondary antibody. The specific
band was detected for thyroglobulin around 300 kDa. (D) Detection of Tg
modification on nitrocellulose membrane probe with streptavidin–HRP.
1
5
6, 12548.
1
1
7 K. K. Sadhu, E. Lindberg and N. Winssinger, Chem. Commun., 2015,
51, 16664.
8 R. M. Yusop, A. Unciti-Broceta, E. M. V. Johansson, R. M. S ´a nchez-
Mart ´ı n and M. Bradley, Nat. Chem., 2011, 3, 239.
41
recruit the cellular machinery and to induce protein degradation.
Given the large number of pathologies associated with the
dysregulation of thyroid hormones, such palladium-driven 19 J. Li, J. Yu, J. Zhao, J. Wang, S. Zheng, S. Lin, L. Chen, M. Yang, S. Jia,
X. Zhang and P. R. Chen, Nat. Chem., 2014, 6, 352.
proteolysis-targeting chimeras approach may constitute a new
2
2
0 A. Dumas and P. Couvreur, Chem. Sci., 2015, 6, 2153.
1 C. D. Spicer, T. Triemer and B. G. Davis, J. Am. Chem. Soc., 2012,
134, 800.
2 J. Li, S. Lin, J. Wang, S. Jia, M. Yang, Z. Hao, X. Zhang and
P. R. Chen, J. Am. Chem. Soc., 2013, 135, 7330.
3 M. A. Miller, B. Askevold, H. Mikula, R. H. Kohler, D. Pirovich and
R. Weissleder, Nat. Commun., 2017, 8, DOI: 10.1038/ncomms15906.
4 A. Dumas, A. Peramo, D. Desma ¨e le and P. Couvreur, Chimia, 2016,
therapeutic tool. The transfer of this approach to now routinely
used genetically-encoded iodinated unnatural amino acids
could also open new perspectives to dissect and manipulate
2
2
2
2
4
0
cellular processes.
The authors thank the Minist `e re de la Recherche et de la
Technologie (fellowship to A. P.), the Fondation pour la
Recherche M ´e dicale (FRM 2018 fellowship to A. P.), the ANR for
70, 252.
5 H. K. Makadia and S. J. Siegel, Polymers, 2011, 3, 1377.
Labex NanoSaclay, ANR-10-LABX-0035 grant, the Swiss National 26 F. Ksar, G. K. Sharma, F. Audonnet, P. Beaunier and H. Remita,
Nanotechnology, 2011, 22, DOI: 10.1088/0957-4484/22/30/305609.
7 J. Belloni, M. Mostafavi, H. Remita, J.-L. Marignier and M.-O. Delcourt,
New J. Chem., 1998, 22, 1239.
Science Foundation (fellowship to A. D.), P. Beaunier from the
Laboratoire de R ´e activit ´e de Surface, (UMR CNRS 7197, Sorbonne
2
Universit ´e , F-75005) for the TEM images and https://smart.servier. 28 S. V. Chankeshwara, E. Indrigo and M. Bradley, Curr. Opin. Chem.
Biol., 2014, 21, 128.
9 A. Nemamcha, H. Moumeni and J. L. Rehspringer, Phys. Procedia,
com/ for the cartoon used in this publication.
2
2
009, 2, 713.
3
3
0 Y. Li, E. Boone and M. A. El-Sayed, Langmuir, 2002, 18, 4921.
1 Y. Noguchi, N. Harii, C. Giuliani, I. Tatsuno, K. Suzuki and
L. D. Kohn, Biochem. Biophys. Res. Commun., 2010, 391, 890.
2 F. Gentile and V. Pansini, Eur. J. Biochem., 1993, 621, 603.
3 F. Gentile, P. Ferranti, G. Mamone, A. Malorni and G. Salvatore,
J. Biol. Chem., 2002, 272, 639.
Conflicts of interest
There are no conflicts to declare.
3
3
Notes and references
34 A. Dedieu, J. C. Gaillard, T. Pourcher, E. Darrouzet and J. Armengaud,
1
2
3
E. M. Sletten and C. R. Bertozzi, Angew. Chem., Int. Ed., 2009, 48, 6974.
M. Grammel and H. C. Hang, Nat. Chem. Biol., 2013, 9, 475.
J. Biol. Chem., 2011, 286, 259.
35 R. Craig and R. C. Beavis, Bioinformatics, 2004, 20, 1466.
H.-W. Shih, D. N. Kamber and J. A. Prescher, Curr. Opin. Chem. Biol., 36 J. A. Stewart, B. F. Piligian, S. R. Rundell and B. M. Swarts, Chem.
2
014, 21, 103.
Commun., 2015, 51, 17600.
4
5
6
M. Yang, J. Li and P. R. Chen, Chem. Soc. Rev., 2014, 43, 6511.
O. Boutureira and G. J. L. Bernardes, Chem. Rev., 2015, 115, 2174.
V. Hong, S. I. Presolski, C. Ma and M. G. Finn, Angew. Chem., Int. Ed.,
37 H. Li and Z. Liu, Trends Anal. Chem., 2012, 37, 148.
38 A. M. Azevedo, A. G. Gomes, L. Borlido, I. F. S. Santos, D. M. F.
Prazeres and M. R. Aires-Barros, J. Mol. Recognit., 2010, 23, 569.
39 D. P. Carvalho and C. Dupuy, Mol. Cell. Endocrinol., 2017, 458, 6.
2
009, 48, 9879.
7
J. M. Baskin, J. A. Prescher, S. T. Laughlin, N. J. Agard, P. V. Chang, 40 S. V. Sharma, X. Tong, C. Pubill-Ulldemolins, C. Cartmell, E. J. A.
I. A. Miller, A. Lo, J. A. Codelli and C. R. Bertozzi, Proc. Natl. Acad.
Sci. U. S. A., 2007, 104, 16793.
Bogosyan, E. J. Rackham, E. Marelli, R. B. Hamed and R. J. M. Goss,
Nat. Commun., 2017, 8, DOI: 10.1038/s41467-017-00194-3.
8
M. F. Debets, S. S. Van Berkel, J. Dommerholt, A. J. Dirks, F. P. J. T. 41 H. Peia, Y. Peng, Q. Zhao and Y. Chen, RSC Adv., 2019, 9,
Rutjes and F. L. Van Delft, Acc. Chem. Res., 2011, 44, 805. 16967–16976.
1
5124 | Chem. Commun., 2019, 55, 15121--15124
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