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Depsipeptides and peptide-mimetics, cyclics and acyclics, integrin αVβ3 inhibitors.
1 , * 2 , 2 , 3 , 2
1  Department of Organic Chemistry II, University of the Basque Country UPV/EHU, 48940, Bilbao, Spain.
2  Departamento de Química Orgánica I, Facultad de Química, Universidad del País Vasco, Manuel Lardizabal 3, 20018 Donostia, Spain
3  GENETADI Biotech, Parque Teconologico 502 Derio-BILBAO (SPAIN) 48160 Spain


Angiogenesis, the sprouting of new blood vessels from pre-existing vessels, is a remarkable feature of tumours growth and metastasis. The in vivo inhibition of this receptor by cyclic peptides containing RGD sequence may be used to selectively suppress these disease1. Our research group has developed a new methodology2 for the evaluation of new antiangiogenic compounds, based in the genetic expression analysis using CGH array system. The RGD mimetics activity can be modified by the presence of ester-bond3, Therefore, we decided to prepare some depsipeptides analogous to the RGD-β-lactam compounds and evaluate their activity performing a genetic expression analysis. We also have evaluated the activity of open-chain compounds without RGD formal structure. The cyclic depsipeptides have demonstrated a very effective inhibitory activity. In the other hand the open-chain compounds have a surprising behavior, demonstrating a similar gene activation. This way, we call into question the essential need of RGD sequence to have an interaction between ligand and the receptor of the integrin4, 5.

  1. da Ressurreicao, A. S. M.; Vidu, A.; Civera M.; Belvisi L.; Potenza, D.; Manzoni, L.; Ongeri, S.; Gennari, C.; Piarulli, U.; Eur. 2009, 15, 12184.
  2. Aizpurua, J. M.; Ganboa, J. I.; Palomo, C.; Loinaz, I.; Oyarbide, J.; Fernandez, X.; Belentová, E.; Fratila, R. M.; Jiménez A.; Miranda, J. I.; Laso, A.; Ávila, S.; Castrillo, J. L.; ChemBioChem, 2001, 11, 401.
  3. Cupido, T.; Spengler, J.; Ruiz-Rodriguez, J.; Adan, J.; Mitjans, F.; Puilats, J.; Albericio, F.; Chem. Int. Ed., 2010, 49, 2732.
  4. Xiong, J. P.; Stehle, T.; Zhang, R.; Joachimiak, A.; Frech, M.; Goodman, S. L.; Arnaout, M. A.; Science, 2002, 296, 151.
  5. Craig, D.; Gao, M.; Schulten, K.; Vogel, V.; Structure, 2004, 12, 2049.
Keywords: Desipeptides; Peptide-mimetics; Integrin inhibitors