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Online ISSN: 1860-7187
October 18, 2011
VIP: Development of Isoxazoline-Containing Peptidomimetics as Dual αvβ3 and α5β1 Integrin Ligands
Alessandra Tolomelli,* Luca Gentilucci, Elisa Mosconi, Angelo Viola, Samantha Deianira Dattoli, Monica Baiula, Santi Spampinato, Laura Belvisi, Monica Civera
The complex mechanisms of cell–cell and cell–matrix adhesion are crucial for developmental processes. The integrin receptors are a large family of transmembrane glycoproteins that mediate these important biological interactions. Among them, integrins αvβ3 and α5β1 are very attractive targets for antitumor therapies, as both subtypes have tumor-specific qualities: the former is expressed at low levels in healthy tissues but is overexpressed in certain cancers, the latter is involved in tumor cell migration, and both play roles in angiogenic processes. Therefore, ligands that simultaneously address both receptor subtypes could be instrumental in combating certain cancer types.
Alessandra Tolomelli and collaborators at the Universities of Bologna and Milan in Italy developed isoxazoline-containing peptidomimetics as effective αvβ3 and α5β1 integrin ligands. Results of their cell adhesion assays suggest a very effective ligand–receptor interaction, as subsequently confirmed by docking studies. The new compounds reported will likely serve as crucial leads for the development of anticancer therapeutic and diagnostic tools.
Received July 30, 2011; published online September 26, 2011, DOI: 10.1002/cmdc.201100372.