ChemComm
Communication
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In the H NMR spectrum of compound 14, resonances due to
T. K. Christopoulos, Clin. Chem., 1991, 37, 625–636; (e) F. Albericio,
Curr. Opin. Chem. Biol., 2004, 8, 211–221; ( f ) R. J. Clark and
D. J. Craik, Biopolymers, 2010, 94, 414–422; (g) C. W. Tornøe,
C. Christensen and M. Meldal, J. Org. Chem., 2002, 67, 3057–3064;
(h) Z. P. Demko and K. B. Sharpless, Angew. Chem., Int. Ed., 2002, 41,
2110–2113; (i) R. Dominique, S. K. Das and R. Roy, Chem. Commun.,
acetyl groups of the sugar moiety were observed as three singlets
around 2.10 ppm, methyl ester of the peptide was noticed as a
singlet around 3.75 ppm and those of the NBD nucleus were
identified around 6.28 and 8.53 ppm. Furthermore, ternary
conjugates 14 showed fluorescence emission lmax at 528 nm
matching with that of the NBD-ester 13. It is appealing to observe
that the fluorescence emission lmax at 572 nm corresponding
to the tetrazine moiety of binary conjugate 12 disappeared
and hence confirming the formation of ternary conjugates 14
1
0
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998, 2437–2438; ( j) R. K. V. Lim and Q. Lin, Chem. Commun., 2010,
46, 1589–1600; (k) C. E. Hoyle and C. N. Bowman, Angew. Chem., Int.
Ed., 2010, 49, 1540–1573.
(a) M. L. Blackman, M. Royzen and J. M. Fox, J. Am. Chem. Soc., 2008,
4
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30, 13518–13519; (b) N. K. Devaraj, R. Weissleder and S. A.
Hilderbrand, Bioconjugate Chem., 2008, 19, 2297–2299; (c) C. M. Cole,
ˇ ˘
J. Yang, J. Seckutec and N. D. Devaraj, ChemBioChem, 2013, 14,
05–208; (d) J. D. Thomas, H. Cui, P. J. North, T. Hofer, C. Rader
2
(
Scheme 3C).
and T. R. Burke, Bioconjugate Chem., 2012, 23, 2007–2013; (e) J. Schoch,
M. Staudt, A. Samanta, M. Wiessler and A. J ¨a schke, Bioconjugate Chem.,
2012, 23, 1382–1386; ( f ) E. Kaya, M. Vrabel, C. Deiml, S. Prill,
V. S. Fluxa and T. Carell, Angew Chem., Int. Ed., 2012, 51, 4466–4469;
In summary, salient features of tetrazine chemistry were
exploited for the synthesis of ternary conjugates. Binary homo-
and hetero-dimeric glycoconjugates are prepared by reaction of
mercaptoethyl or hydroxyethyl saccharides and the ternary
conjugation was performed by inverse electron demand Diels–
Alder reaction of the tetrazine nucleus. The method is modular
and thus a suite of molecules can participate in ternary
conjugation.
(
2
g) C. F. Hansell, P. Espeel and M. M. Stamenovi ´c , J. Am. Chem. Soc.,
011, 133, 13828–13831; (h) J. Malinge, C. Allain, L. Galmiche,
F. Miomandre and P. Audebert, Chem. Mater., 2011, 23, 4599–4605.
(a) T. C. Shiao and R. Roy, New J. Chem., 2012, 36, 324–339; (b) J. Sebestik,
P. Niederhafner and J. Jezek, Amino Acids, 2011, 40, 301–370;
5
(
c) A. Dondoni and A. Marra, Chem. Rev., 2010, 110, 4949–4977.
6 (a) P. H. Seeberger, Chem. Commun., 2003, 1115–1121; (b) R. A.
Dwek, Chem. Rev., 1996, 96, 683–720; (c) P. M. Rudd, T. Elliott,
P. Cresswell, I. A. Wilson and R. A. Dwek, Science, 2001, 291,
S.H. thanks the DST, New Delhi, for the SwarnaJayanthi
Fellowship and B.V.R. thanks CSIR for the financial support.
2370–2376.
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(a) W. R. Algar, D. E. Prasuhn, M. H. Stewart, T. J. Jennings,
J. B. Blanco-Canosa, P. E. Dawson and I. L. Medintz, Bioconjugate
Chem., 2011, 22, 825–858; (b) I. K. Guttilla and B. A. White, J. Biol.
Chem., 2009, 284, 23204–23216; (c) C. L. Choi and A. P. Alivisatos,
Annu. Rev. Phys. Chem., 2010, 61, 369–389; (d) L. I. Willems, N. Li,
B. I. Florea, M. Ruben, G. A. Van der Marel and H. S. Overkleeft,
Angew. Chem., Int. Ed., 2012, 51, 4431–4434.
References
1
C. I. Schilling, N. Jung, M. Biskup, U. Schepers and S. Brase, Chem.
Soc. Rev., 2011, 40, 4840–4871.
2
(a) T. Clackson, in Chemical Biology: From Small Molecules to Systems
Biology and Drug Design, ed. S. L. Schreiber, T. M. Kapoor and
G. Wess, Wiley-VCH Verlag GmbH, Weinheim, Germany, 2008,
ch. 4b; (b) P. A. Hessian and L. Fisher, Eur. J. Biochem., 2001, 268,
8 (a) M. D. Coburn, G. A. Buntain, B. W. Harris, M. A. Hiskey, K. Y. Lee
and D. G. Ott, J. Heterocycl. Chem., 1991, 28, 2049–2050; (b) D. E.
Chavez and M. A. Hiskey, J. Heterocycl. Chem., 1998, 35, 1329–1332;
(c) M. D. Helm, A. Plant and J. P. A. Harrity, Org. Biomol. Chem.,
2006, 4, 4278–4280.
3
2
53–363; (c) A. Rutkowska and C. Schultz, Angew. Chem., Int. Ed.,
012, 51, 8166–8176; (d) R. Roy, in Carbohydrate Chemistry, ed.
G. J. Boons, Chapman and Hall, UK, 1998, pp. 243–321.
(a) E. M. Sletten and C. R. Bertozzi, Angew. Chem., Int. Ed., 2009, 48,
3
9 G. Clavier and P. Audebert, Chem. Rev., 2010, 110, 3299–3314.
6
2
974–6998; (b) E. Saxon and C. R. Bertozzi, Science, 2000, 287, 10 See ESI‡.
007–2010; (c) J. A. Link, M. L. Mock and D. A. Tirrell, Curr. 11 M. J. Tucker, J. R. Courter, J. Chen, O. Atasoylu, A. B. Smith III and
Opin. Biotechnol., 2003, 14, 603–609; (d) E. P. Diamandis and
R. M. Hochstrasser, Angew. Chem., Int. Ed., 2010, 49, 3612–3616.
This journal is c The Royal Society of Chemistry 2013
Chem. Commun.