10.1002/chem.201703093
Chemistry - A European Journal
COMMUNICATION
valuable tool to enhance the integrin targeting performance of
this kind of conjugates, and may represent a possible way to
improve the in vivo tumor targeting properties of RGD
conjugates, which are often suboptimal.[3b,3d,3h,6e] Moreover, it
should be noted that the new ligands are also suitable for
conjugation to different kinds of ‘smart’ linkers such as those
amenable to extracellular cleavage[20] (for example by matrix
metalloproteinases[21] or elastases[22]).
H. Zhao, Z. Liu, F. Wang, X. Chen, S. Liu, Mol. Pharm. 2009, 6, 231-
245; e) S. Liu, Bioconjugate Chem. 2015, 26, 1413-1438; f) V. López-
Rodríguez, C. Galindo-Sarco, F. O. García-Pérez, G. Ferro-Flores, O.
Arrieta, M. A. Ávila-Rodríguez, J. Nucl. Med. 2016, 57, 404-409; g) C.
Zhai, G. M. Franssen, M. Petrik, P. Laverman, D. Summer, C. Rangger,
R. Haubner, H. Haas, C. Decristoforo, Mol. Imaging Biol. 2016, 18, 758-
767; h) C. Imberti, S. Y. A. Terry, C. Cullinane, F. Clarke, G. H.
Cornish, N. K. Ramakrishnan, P. Roselt, A. P. Cope, R. J. Hicks, P. J.
Blower, M. T. Ma, Bioconjugate Chem. 2017, 28, 481-495.
Experimental Section
[4]
a) B. C. Lee, B. S. Moon, J. S. Kim, J. H. Jung, H. S. Park, J. A.
Katzenellenbogen, S. E. Kim, RSC Advances 2013, 3, 782-792; b) M. H.
Lee, J. L. Sessler, J. S. Kim, Acc. Chem. Res. 2015, 48, 2935-2946; c)
Z.-H. Jin, T. Furukawa, M. Degardin, A. Sugyo, A. B. Tsuji, T.
Yamasaki, K. Kawamura, Y. Fujibayashi, M.-R. Zhang, D. Boturyn, P.
Dumy, T. Saga, Mol. Cancer Ther. 2016, 15, 2076-2085.
Cyclo[DKP-RGD]-CH2NH2 (2),[9] Fmoc-Val-Ala-N-[4-[[[(N-(Boc)-N,N’-
dimethylethylenediamine)carbonyl]oxy]methyl]phenyl] (15)[12] and 2’-(4-
nitrophenoxycarbonyl)paclitaxel (17),[12] were prepared according to
literature procedures, and their analytical data were in agreement with
those already published. The synthetic procedures for the preparation of
compounds 5-9 and 11-14 are reported in the Supporting Information,
along with the 1H NMR and 13C NMR spectra, the HPLC traces and
HRMS spectra. The inhibition assays of biotinylated vitronectin binding to
the v3 receptor for compounds 1 and 5-9 are reported in the Supporting
Information.
[5]
a) R. Mahato, W. Tai, K. Cheng, Adv. Drug Delivery Rev. 2011, 63,
659-670; b) T. Lammers, F. Kiessling, W. E. Hennink, G. Storm, J.
Control. Release 2012, 161, 175-187; c) N. Krall, J. Scheuermann, D.
Neri, Angew. Chem. Int. Ed. 2013, 52, 1384-1402; Angew. Chem.
2013, 125, 1424-1443; d) G. Casi, D. Neri, J. Med. Chem. 2015, 58,
8751-8761; e) P. T. Wong, S. K. Choi, Chem. Rev. 2015, 115, 3388-
3432.
Acknowledgements
We thank the University of Milan for PhD fellowships (to A.P.
and A.D.C.) and the European Commission (Marie Skłodowska-
Curie ITN MAGICBULLET 642004) for a PhD fellowship (to
A.R.M.D.) and financial support. We also gratefully acknowledge
Ministero dell’Università e della Ricerca (PRIN 2015 project
20157WW5EH) for financial support.
[6]
For the use of RGD peptides and peptidomimetics as carriers of
nanoparticles, imaging agents and anticancer drugs, see: a) F. Danhier,
A. Le Breton, V. Préat, Mol. Pharm. 2012, 9, 2961-2973; b) D. Arosio,
C. Casagrande,L. Manzoni, Curr. Med. Chem. 2012, 19, 3128-3151; c)
F. C. Gaertner, H. Kessler, H.-J. Wester, M. Schwaiger,A. J. Beer, Eur.
J. Nucl. Med. Mol. Imaging 2012, 39, 126-138; d) N. Anwar, A. Rix, W.
Lederle, A. J. C. Kuehne, Chem. Commun. 2015, 51, 9358-9361; e) A.
Dal Corso, L. Pignataro, L. Belvisi, C. Gennari, Curr. Top. Med. Chem.
2016, 16, 314-329; f) D. Arosio, C. Casagrande, Advanced Drug
Delivery Reviews 2016, 97, 111-143; g) D. Arosio, L. Manzoni, C.
Corno, P. Perego, Recent Pat Anticancer Drug Discov. 2017, 12, 148-
168.
Keywords: antitumor agents • click chemistry • integrins •
multivalency • peptidomimetics
[1]
a) A. Barnard, D. K. Smith, Angew. Chem. Int. Ed. 2012, 51, 6572-
6581; Angew. Chem. 2012, 124, 6676-6685; b) C. Fasting, C. A.
Schalley, M. Weber, O. Seitz, S. Hecht, B. Koksch, J. Dernedde, C.
Graf, E.-W. Knapp, R. Haag, Angew. Chem. Int. Ed. 2012, 51, 10472-
10498; Angew. Chem. 2012, 124, 10622-10650; c) E. Mahon, M.
Barboiu, Org. Biomol. Chem. 2015, 13, 10590-10599.
[7]
[8]
[9]
a) M. Schottelius, B. Laufer, H. Kessler, H.-J. Wester, Acc. Chem. Res.
2009, 42, 969-980; b) M. Sutherland, A. Gordon, S. D. Shnyder, L. H.
Patterson, H. M. Sheldrake, Cancers 2012, 4, 1106-1145.
M. Marchini, M. Mingozzi, R. Colombo, I. Guzzetti, L. Belvisi, F. Vasile,
D. Potenza, U. Piarulli, D. Arosio, C. Gennari, Chem. Eur. J. 2012, 18,
6195-6207.
[2]
a) M. Janssen, W. J. G. Oyen, L. F. A. G. Massuger, C. Frielink, I.
Dijkgraaf, D. S. Edwards, M. Radjopadhye, F. H. M. Corstens,O. C.
Boerman, Cancer Biother. Radiopharm. 2002, 17, 641-646; b) G.
Thumshirn, U. Hersel, S. L. Goodman, H. Kessler, Chem. Eur. J. 2003,
9, 2717-2725; c) E. R. Gillies, J. M. J. Fréchet, Drug Discovery Today
2005, 10, 35-43; d) E. Garanger, D. Boturyn, J. L. Coll, M. C. Favrot, P.
Dumy, Org. Biomol. Chem. 2006, 4, 1958-1965; e) S. M. Deyev, E. N.
Lebedenko, BioEssays 2008, 30, 904-918; f) D. J. Welsh, D. K. Smith,
Org. Biomol. Chem. 2011, 9, 4795-4801; g) D. S. Choi, H.-E. Jin, S. Y.
Yoo, S.-W. Lee, Bioconjugate Chem. 2014, 25, 216-223; h) N. Krall, F.
Pretto, D. Neri, Chem. Sci. 2014, 5, 3640-3644; i) A. Bianchi, D. Arosio,
P. Perego, M. De Cesare, N. Carenini, N. Zaffaroni, M. De Matteo, L.
Manzoni, Org. Biomol. Chem. 2015, 13, 7530-7541.
R. Colombo, M. Mingozzi, L. Belvisi, D. Arosio, U. Piarulli, N. Carenini,
P. Perego, N. Zaffaroni, M. De Cesare, V. Castiglioni, E. Scanziani, C.
Gennari, J. Med. Chem. 2012, 55, 10460-10474.
[10] M. Mingozzi, L. Manzoni, D. Arosio, A. Dal Corso, M. Manzotti, F.
Innamorati, L. Pignataro, D. Lecis, D. Delia, P. Seneci, C. Gennari, Org.
Biomol. Chem. 2014, 12, 3288-3302.
[11] S. Zanella, M. Mingozzi, A. Dal Corso, R. Fanelli, D. Arosio, M.
Cosentino, L. Schembri, F. Marino, M. De Zotti, F. Formaggio, L.
Pignataro, L. Belvisi, U. Piarulli, C. Gennari, ChemistryOpen 2015, 4,
633-641.
[12] a) A. Dal Corso, M. Caruso, L. Belvisi, D. Arosio, U. Piarulli, C.
Albanese, F. Gasparri, A. Marsiglio, F. Sola, S. Troiani, B. Valsasina, L.
Pignataro, D. Donati, C. Gennari, Chem. Eur. J. 2015, 21, 6921-6929;
b) S. Zanella, S. Angerani, A. Pina, P. López Rivas, C. Giannini, S.
Panzeri, D. Arosio, M. Caruso, F. Gasparri, I. Fraietta, C. Albanese, A.
Marsiglio, L. Pignataro, L. Belvisi, U. Piarulli, C. Gennari, Chem. Eur. J.
2017, 23, 7910-7914.
[3]
a) D. Boturyn, J. L. Coll, E. Garanger, M. C. Favrot, P. Dumy, J. Am.
Chem. Soc. 2004, 126, 5730-5739; b) J. Shi, L. Wang, Y.-S. Kim, S.
Zhai, Z. Liu, X. Chen, S. Liu, J. Med. Chem. 2008, 51, 7980-7990; c) L.
Sancey, E. Garanger, S. Foillard, G. Schoehn, A. Hurbin, C. Albiges-
Rizo, D. Boturyn, C. Souchier, A. Grichine, P. Dumy, J. L. Coll, Mol.
Ther. 2009, 17, 837-843; d) L. Wang, J. Shi, Y.-S. Kim, S. Zhai, B. Jia,
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