In silico studies, synthesis and binding evaluation of substituted 2-pyrrolidinones as peptidomimetics of RGD tripeptide sequence

•In silico optimisation of a new family of peptidomimetics of RGD is presented.•Synthesis of optimised peptidomimetics of RGD is developed.•Binding evaluation of αvβ3 integrin affinity is presented.

In silico optimisation, synthesis and binding evaluation of αvβ3 integrin's affinity for precursors of a new RGD peptidomimetics family are presented. The 2-pyrrolidinone building block was obtained by condensation of l-lysine with dimethoxydihydrofuran followed by reduction. The ring was functionalized with a carboxylic acid and a guanidinium appendage. On the pyrrolidinone heterocycle, the effects on affinity of position, length and relative geometry of the two acid or basic functionalized side chains introduced on the pyrrolidinone ring have been previously evaluated by docking studies. Peptidomimetics have finally been evaluated by competition binding assays for αvβ3 integrin's affinity using radio-ligands.

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