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Séminaire Chimie ED459

Synthesis and biomedical applications of tumor targeting integrin ligands and conjugates

Prof. Umberto Piarulli (Dipartimento di Scienza e Alta Tecnologia, Università degli Studi dell’Insubria, Como, Italy)

publié le

Le Jeudi 19 novembre 2015 à 13h45
UM FdS, Salle de Cours SC-16.01

The importance and specificity of protein associations in cellular events and in the etiology of many pathologic processes raised interest on protein-protein interactions as attractive targets for therapeutic intervention. In cancer, several cell surface protein receptors, such as the αVβ3, αVβ5 and α5β1 integrins, are considered specific molecular indicators of tumor angiogenesis, progression and metastasis. In addition, these receptors represent an interesting target for tumor-homing peptides, which can act as vectors of cytotoxic payload directly to tumour cells.

We have recently investigated the synthesis and the biological properties of a new class of cyclic peptidomimetics containing a bifunctional diketopiperazine (DKP) scaffold and the tripeptide sequence Arg-Gly-Asp (RGD) [1] or isoAsp-Gly-Arg (isoDGR) [2] as potent integrin ligands. The interaction of cyclo[DKP-RGD] ligands with intact cancer cells was investigated [3] and these ligands showed effective inhibition of angiogenesis in HUVEC cells without affecting cell viability and proliferation [4].

A small number of cyclo[DKP-RGD]-Paclitaxel conjugates were synthesized and the cytotoxicity and targeting properties of these constructs were determined [5].

Scheme 1 (click for full view)


1. 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. S. Panzeri, S. Zanella, D. Arosio, L. Vahdati, A. Dal Corso, L. Pignataro, M. Paolillo, S. Schinelli, L. Belvisi, C. Gennari, U. Piarulli, Chem. - Eur. J. 2015, 21, 6265–6271.
3. I. Guzzetti, M. Civera, F. Vasile, E. M. Araldi, L. Belvisi, C. Gennari, D. Potenza, R. Fanelli, U. Piarulli, Org. Biomol. Chem. 2013, 11, 3886–3893.
4. R. Fanelli, L. Schembri, U. Piarulli, M. Pinoli, E. Rasini, M. Paolillo, M. C. Galiazzo, M. Cosentino, F. Marino, Vascular Cell, 2014, 6, 11.
5. a) 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 ; b) 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.

Contact local IBMM : Dr. Florine Cavelier, D.R. CNRS (DAPP)


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