The chiral cyclobutane motif in the synthesis of dendrimers and multifunctional platforms. Applications as contrat agents cell-penetrating peptides, and NPY analogues

Abstract

The present doctoral thesis has been developed in the context of the Synthesis, Structure and Chemical Reactivity research group. Taking advantage of the broad experience of this group in the synthesis of highly constrained cyclobutane amino acids and their inclusion into peptides, a series of new compounds with potential very interesting applications have been prepared: Cyclobutane ring has been both used as core and dendron for the synthesis of a first generation family of chiral peptide dendrimers. The capability of the four-membered ring to induce defined secondary structures has been exploited in the preparation of hybrid cyclobutane-proline ¿,¿-peptides which were suitable for their evaluation as Cell Penetrating Peptides (CPPs). In an analogous way, a series of cyclobutane-containing NPY analogues have been synthesised. It is expected that the intrinsic ability of the cyclobutane ring to induce defined folding will be useful to mimic NPY bioactive conformation. Furthemore, the possibility of preparing multivalent cyclobutane compounds encouraged us to design new chiral polyfunctional cyclobutane platforms which could lead to a new class of Magnetic Resonance Imaging (MRI) contrast agents (CAs).