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Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Development of isoxazoline-containing peptidomimetics as dual αvβ3 and α5β1 integrin ligands
Alessandra Tolomelli1, Luca Gentilucci, Elisa Mosconi
1Department of Chemistry G. Ciamician, University of Bologna, Via Selmi 2, 40126 Bologna, Italy. alessandra.tolomelli@unibo.it
Abstract:
Isoxazoline-containing peptidomimetics, designed to be effective α(v)β(3) and α(5)β(1) integrin ligands, were synthesized through an original procedure involving N,O-bis(trimethylsilyl)hydroxyamine conjugate addition to alkylidene acetoacetates, followed by intramolecular hemiketalization. To mimic the RGD recognition sequence, basic and acidic terminal appendages were introduced, and the final products were tested in cell adhesion inhibition assays. All the synthesized compounds proved to be excellent ligands for both integrin receptors, and a strong influence on intracellular signaling and phosphorylation pathways was demonstrated by evaluation of fibronectin-induced phosphorylation of ERK. The molecular basis of the observed inhibitory activity was suggested on the results of docking experiments.
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