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MedChemComm
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DOI: 10.1039/C5MD00508F
COMMUNICATION
Journal Name
min displayed in a bar chart. Errors are given as standard deviation
representing n = 3
stability was observed in human serum at 37 °C over a period
of 1.5h. Further in vitro and in vivo evaluation of the new 18F-
folate using human KB cells and PET imaging are ongoing.
Similarly, investigations and evaluation using the other new
18F-tracers derived from copper-free 18F-click labeling in in vivo
PET imaging are planned.
.
Summarized conditions, RCY and kinetics for the four
biomolecule-azides, which were tested in copper-free click
reactions with the new 18F-prosthetic group are shown in the
ESI. The RCY are also displayed as a bar chart in scheme 4.
Especially for the radiolabeling of sensitive biomolecules, the
use of 18F-prosthetic groups is of particular interest, where the
use of harsh conditions for direct 18F-labeling reactions is
excluded. Due to the toxicity of copper, the attachment of the
18F-prosthetic groups via copper(I)-catalyzed cycloaddition is
no longer the first choice. The use of strained alkynes for
copper-free cycloaddition enables selective radiolabeling of
azido-functionalized biomolecules under very mild conditions.
Notes and references
1
2
3
N. Johnsson and K. Johnsson, ACS Chemical Biology, 2007, 2,
no.1, 31
J. Ermert and H.H. Coenen, Journal of Labelled Compounds
and Radiopharmaceuticals, 2013, 56, no. 3-4, 225
H. H. Coenen, R.H. Elsinga, R. Iwata, M. R. Kilbourn, M. R. a
Pillai, G. R. Rajan, H. N. Wagner and J. J. Zaknun, Nuclear
Medicine and Biology, 2010, 37, no.7, 727
4
5
6
L. Lang and W. C. Eckelman, Applied Radiation and Isotopes,
1994, 45, no.12, 1155
S. Okarvi, European Journal of Nuclear Medicine, 2001, 28
no.7, 929
T. Poethko, M. Schottelius, G. Thumshirn, U. Hersel, M. Herz,
G. Henriksen, H. Kessler, M. Schwaiger and H. Wester, The
Journal of Nuclear Medicine, 2004, 45, 892
,
The herein reported synthesis strategy of a 18F-labeled DBCO-
based prosthetic group enables copper-free 18F-click labeling
of various biomolecule-azides under very mild conditions and
with outstanding efficacy. The organic syntheses provided the
two precursors in good to high yields over four steps. The
organic syntheses are robust and very reliable, and referred to
DBCO-amine, the strategy and yields were optimized for
economic reasons. High to excellent results were obtained for
the 18F-labeling of the two different precursors, which are
available and ready-to-use for subsequent 18F-click reactions
within only 60 min and in high yields of 34% (n.d.c.).
7
T. Priem, C. Bouteiller, D. Camporese, X. Brune, J. Hardouin,
A. Romieu and P.-Y. Renard, Organic & Biomolecular
Chemistry, 2013, 11, no.3, 469
8
9
H.C. Kolb, M.G. Finn and K.B. Sharpless, Angewandte Chemie
International Edition, 2001, 40, 2004 - 2021
R. Huisgen, Angewandte Chemie International Edition, 1963,
2
, no.10, 565
10 J. Marik, J. L. Sutcliffe, Tetrahedron Letters, 2006, 47, 37,
6681-6684
11 K. Kettenbach, H. Schieferstein and T.L. Ross, BioMed
Research International, 2014, 1
12 H. Schieferstein and T. L. Ross, European Journal of Organic
Chemistry, 2014, 3546
13 J.M. Baskin, J.A. Prescher, S.T. Laughlin, N.J. Agard, P.V.
Chang, I.A. Miller, A. Lo, J.A. Codelli, C.R. Bertozzi,
Proceedings of the National Academy of Sciences, 2007, 104
43, 16793-7
14 A. Kuzmin, A. Poloukhtine, M.A. Wolfert, V.V. Popik,
Bioconjugate Chemistry, 2010, 21, 2076-85
15 S. Arumugam, J. Chin, R. Schirmacher, V. V. Popik, A. P.
Kostikov, Bioorganic & Medicinal Chemistry Letters, 2011, 21
no. 23, 6987
16 A. Almutairi, R. Rossin, M. Shokeen, A. Hagooly, A. Ananth, B.
Capoccia, S- Guillaudeu, D. Abendschein, C. J. Anderson, M. J.
Welch and J. M. J. Fre, Proceedings of the National Academy
of Sciences, 2009, 106, no.3, 685
,
The new 18F-prosthetic group performs outstandingly in
copper-free click reactions with different biomolecule-azides,
which are known as excellent tumor targeting vectors of
common interest.23,24,25,16,17 All click reactions proceeded with
excellent to even quantitative yields under very mild
conditions (water or PBS, RT or 40 °C) with very fast reaction
,
kinetics. The tested biomolecule-azides (RGD, linear MSH- 17 Z.-B. Li, Z. Wu, K. Chen, F. T. Chin and X. Chen, Bioconjugate
Chemistry, 2007, 18, no.6, 1987
peptides and folic acid) were not achievable in such good
18 O. Seitz, H. Kunz, Journal of Organic Chemistry, 1997, 62, 813
19 S. A. Campos, J. D. Harling, A. H. Miah and I. E. D. Smith,
Patent, 2014, WO 2014108452 A1
20 S. Keil, C. Claus, W. Dippold and H. Kunz, Angewandte
Chemie International Edition, 2001, 40, no.2, 366
21 Y. Hirata, S. Hosoe, M. Maemoto, M. Sugawara, A.
Yanagisawa, J. Ouchi, Patent, 2013, WO 2013129435 A1
22 M. Amblard, J. Fehrentz, J. Mertinez and G. Subra, Molecular
Biotechnology, 2006, 33, 239
yields
with
conventional
copper(I)-catalyzed
click
cycloaddition.11
In cases of non-quantitative 18F-click labeling, the 18F-labeled
products were easily separated by radio-HPLC from the
unreacted 18F-prostehtic group. For the 18F-labeled folate
derivative a low logD value of 0.6 ± 0.07 was determined. High
23 C. P. Leamon, P. S. Low, Research Focus, 2001, 6446, 2, 44
24 W. Siegrist, F. Solca, S. Stutz, L. Giuffre, S. Carrel, J. Girard
and A. Eberle, Cancer Research, 1989, 49, 6352
4 | J. Name., 2012, 00, 1-3
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