Peptidomimetic Scaffolds for the Discovery of New Bioactive Compounds. Cyclotetrapeptide Analogues Based on a 13-Membered, Partially Modified Retro-Inverso Structure. Applications to the synthesis of Cancer Cell Adhesion Inhibitors

In recent years, we have been interested in cyclic peptides (CP) as restricted mimics of biologically active, naturally occurring peptides, and in particular, we pursued the synthesis of small, conformationally defined CPs or analogues that mimic - or -turns. Among the different members of the CP family, cyclotetrapeptides (CTP) are considered the smallest system which can reproduce all kinds of turns, but their potential utility is often diminished by difficult synthesis and poor conformational stability. To overcame these limitations, we designed a novel family of CTP analogues, based on a 13-membered partially modified retro-inverso (PMRI) structure, built by introduction of a diamine (a -amino acid mimetic) and a diacid, in different positions. The PMRI-CTPs give rise to a higher degree of chemical and spatial diversity respect to normal CTP, and can be utilized as scaffolds for applications in medicinal chemistry