Chemical Science
Edge Article
were in proximity to green-uorescent Iba1 + TAMs, which
suggests their close interaction in aggressive carcinomas.
Whereas further studies will be necessary to characterise the
exact phenotype of TAMs in these tumours, we demonstrate the
utility of the peptide 8 in uorescence imaging studies aimed at
understanding dynamic interactions between immune cells and
cancer cells in tumour tissues in situ.
Notes and references
1 M. Vendrell, D. Zhai, J. C. Er and Y. T. Chang, Chem. Rev.,
2012, 112, 4391–4420.
2 L. Chen, S. Xu, W. Li, T. B. Ren, L. Yuan, S. S. Zhang and
X. Zhang, Chem. Sci., 2019, 10, 9351–9357.
3 H. Li, Y. Li, O. Yao, J. Fan, W. Sun, S. Long, K. Shao, J. Du,
J. Wang and X. Peng, Chem. Sci., 2019, 10, 1619–1625.
4
M. Li, S. Long, Y. Kang, L. Guo, J. Wang, J. Fan, J. Du and
X. Peng, J. Am. Chem. Soc., 2018, 140, 15820–15826.
Conclusions
In summary, we describe the preparation of Trp(redBODIPY) as
the rst red-emitting Trp-based amino acid by Pd-catalysed
5 N. Kielland, M. Vendrell, R. Lavilla and Y. T. Chang, Chem.
Commun., 2011, 48, 7401–7403.
coupling to
a
thiophene-appended BODIPY uorophore.
6 S. J. Park, H. C. Yeo, N. Y. Kang, H. Kim, J. Lin, H. H. Ha,
M. Vendrell, J. S. Lee, Y. Chandran, D. Y. Lee, S. W. Yun
and Y. T. Chang, Stem Cell Res., 2014, 12, 730–741.
7 F. de Moliner, N. Kielland, R. Lavilla and M. Vendrell, Angew.
Chem., Int. Ed., 2017, 56, 3758–3769.
8 C. Zhao, L. Mendive-Tapia and M. Vendrell, Arch. Biochem.
Biophys., 2019, 661, 187–195.
9 D. Wu, H. C. Daly, M. Grossi, E. Conroy, B. Li,
W. M. Gallagher, R. Elmes and D. F. O'Shea, Chem. Sci.,
2019, 10, 6944–6956.
Trp(redBODIPY) is compatible with conventional SPPS proto-
cols and it was used to synthesize a minimally-disrupted KRT1-
binding peptide with red uorogenic properties. Notably, our
computational and experimental data indicates that the incor-
poration of Trp(redBODIPY) within KRT1-binding sequences is
more favourable than the conventional lysine derivatisation
with BODIPY TR, in terms of binding mode, protein affinity
and signal-to-noise ratios. Finally, we used the Trp(redBODIPY)-
labelled cyclopeptide 8 for live-cell and ex vivo imaging of
KRT1+ cancer cells and to study their interactions with tumour- 10 A. H. Harkiss and A. Sutherland, Org. Biomol. Chem., 2016,
associated macrophages in aggressive carcinomas.
14, 8911–8921.
11 P. Cheruku, J. H. Huang, H. J. Yen, R. S. Iyer, K. D. Rector,
J. S. Martinez and H. L. Wang, Chem. Sci., 2015, 6, 1150–
Ethical statement
1158.
This study was performed in strict accordance with the guide- 12 J. Ge, L. Li and S. Q. Yao, Chem. Commun., 2010, 47, 10939–
lines on the United Kingdom Animals Act 1986 for the care and
10941.
use of laboratory animals. The work was approved by the Home 13 A. H. Harkiss, J. D. Bell, A. Knuhtsen, A. G. Jamieson and
Office (Animals in Science Regulation Unit) and performed
A. Sutherland, J. Org. Chem., 2019, 84, 2879–2890.
under the local rules and guidance of the Animal Welfare and 14 A. V. Strizhak, V. Y. Postupalenko, V. V. Shvadchak,
Ethical Review Body at The University of Edinburgh (Edinburgh,
UK), which is a designated User and Supplying Establishment
under ASPA (1986) with PEL number 60/6205.
N.
Morellet,
E.
Guittet,
V.
G.
Pivovarenko,
A. S. Klymchenko and Y. M ´e ly, Bioconjugate Chem., 2012,
23, 2434–2443.
1
5 L. Mendive-Tapia, C. Zhao, A. R. Akram, S. Preciado,
F. Albericio, M. Lee, A. Serrels, N. Kielland, N. D. Read,
R. Lavilla and M. Vendrell, Nat. Commun., 2016, 7, 10940.
Conflicts of interest
The authors declare no conicts of interest.
16 L. Mendive-Tapia, R. Subiros-Funosas, C. Zhao, F. Albericio,
N. D. Read, R. Lavilla and M. Vendrell, Nat. Protoc., 2017, 12,
1588–1619.
Acknowledgements
1
7 R. Subiros-Funosas, L. Mendive-Tapia, J. Sot, J. D. Pound,
N. D. Barth, Y. Varela, F. M. Go n˜ i, M. Paterson,
C. D. Gregory, F. Albericio, I. Dranseld, R. Lavilla and
M. Vendrell, Chem. Commun., 2017, 53, 945–948.
R. S. F acknowledges a MSCA Individual Fellowship (659046). N.
D. B. acknowledges funding from OPTIMA (EP/L016559/
1). L. M. T. acknowledges the support of Fundacion Antonio
Martin Escudero (FAME) in the form of a post-doctoral fellow- 18 B. Weigelt, J. L. Peterse and L. J. Van't Veer, Nat. Rev. Cancer,
ship. B. Q. acknowledges funds from a CRUK Career Develop-
2005, 5, 591–602.
ment Fellowship (C49791/A17367) and an ERC Starting Grant 19 A. Poellinger, J. Biophotonics, 2012, 5, 815–826.
716379). R. L. acknowledges support from the Ministerio de 20 J. S. Drukteinis, B. P. Mooney, C. I. Flowers and
Econom ´ı a y Competitividad-Spain (CTQ2015-67870-P, ERA-NET
R. A. Gatenby, Am. J. Med., 2013, 126, 472–479.
PCIN-2015-224), Generalitat de Catalunya (2017 SGR 21 B. B. Koolen, W. V. Vogel, M. J. Vrancken Peeters, C. E. Loo,
(
1439). M. V. acknowledges funds from an ERC Consolidator
E. J. T. Rutgers and R. A. Vald ´e s Olmos, J. Oncol., 2012, 2012,
Grant (771443) and Wellcome Trust iTPA (PIII-006). The authors
438647.
acknowledge support from EP/M507258/1 (Equipment grant) 22 Q. T. Nguyen, E. S. Olson, T. A. Aguilera, T. Jiang,
and thank the technical support from the Flow Cytometry and
the Confocal Advanced Light Microscopy units at the University
of Edinburgh.
M. Scadeng, L. G. Ellies and R. Y. Tsien, Proc. Natl. Acad.
Sci. U. S. A., 2010, 107, 4317–4322.
Chem. Sci.
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