Synthesis of linear and cyclic peptides for therapeutic targets

Abstract

In the last decades, peptides have attracted a growing interest in therapeutic applications thanks to their high affinity and specificity, high tissue penetration and chemical stability. Moreover, they can be easily chemically synthetised and modified. Peptides can achieve their therapeutic effect either binding a protein pocket, similar to small molecules, or interact with a protein surface, similar to antibodies. In base of their origin, peptides can be defined as natural or synthetic. In the following work, we synthetised and purified the natural linear peptide B18, derived from the human protein BST-2 and the synthetic cyclic peptide PT4, an inhibitor of GES-5 β-lactamases. B18 could be applied as an inhibitor of metastasis formation in specific tumours, such as breast cancer, lung cancer, oral cavity cancers, head and neck carcinomas, endometrial cancer, glioblastomas, and lymphomas. While PT4 could be used in the treatments for antibiotic resistance to carbapenems. The peptides were synthesised via automatised Fmoc-solid-phase peptide synthesis and purified via reverse phase HPLC, in order to remove impurities and truncated forms. The purity and the final mass were assessed by LC-MS.