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Targeting integrins and beyond: synthesis and functional assessment of multi-task peptidomimetic assemblies as new therapeutic and diagnostic tools

Integrins are cell surface receptors playing essential roles in many physiological and pathological events. The relevance of RGD-dependent αVβ3, αVβ5, αVβ6 and α5β1 integrins during tumour angiogenesis and tumour development is well established. This is also reflected by differential integrin expression patterns in normal versus tumour tissue as well as in different stages of tumour progression.

In recent years our efforts in the area of specific integrin ligands led to the development of a new series of γ-aminocyclopentanecarboxylic acid (Acpca)-based or γ-aminoproline (Amp)-based RGD-cyclotetrapeptides which turned out to be very potent αVβ3, αVβ5 and α5β1 integrin binders with IC50 binding affinities in the nanomolar range. In particular, the covalent conjugation of our AmpRGD ligands with cytotoxic agents or diagnostic probes such as fluorescent probes or metal-chelating units (e.g. DOTA), as well as their embodiment in liposomal nanoparticles were accomplished and biological properties of these bioconjugates were evaluated with encouraging results.

Focus of this research line is on the design, synthesis, and characterisation of novel and modulable integrin-targeted RGD-based pseudopeptide ligands and their conjugates for molecular recognition and biomedical applications in the field of target-directed anti-cancer therapy and non-invasive diagnosis.

More recently, our research interest moved to the α4β1 integrin subfamily, which covers a prime role among the therapeutic targets of interest in fighting multiple sclerosis. The aim of our project is to design and synthesize a new class of small-molecule peptidomimetics able to effectively bind to the α4β1 receptor in order to interfere with the migration of lymphocytes T across the BBB with subsequent demyelinating effect.


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Representation of the AmpRGD ligand PRGC031 docked into the binding region of αVβ3 integrin.
 Radiolabeled AmpRGD ligand PRGC044
Pubblicato Wednesday, 11 June, 2014 - 12:23 | ultima modifica Thursday, 26 January, 2017 - 12:29