Structure and activity of cyclo-tetrapeptides

Peptide-based therapies currently show an exciting renaissance of interest due to bio-technological advances, which lead to overcome peptide limitations, improving their ADME profile. Short cyclic peptides have gained a growing attention as valuable therapeutics because of their unique structures and appealing biological features such as increased bio-stability, membrane permeability, and bioavailability. It is noteworthy that peptides are the most versatile motifs offering much more functional and structural diversity than any other molecule. The function of these important biomolecules in bio-processes, and constituents of proteins, can hardly be mimicked by other chemical compounds. Thanks to recent achievements in diverse fields of science, peptides will revolutionize medicine soon, in the relation of either smart theranostics, vaccines, drug/gene delivery systems or bio-functional nanomaterials.

Our project focuses on the design, synthesis, molecular and supramolecular studies on biologically active ultra-short peptides. Here, we will present results of investigation of selected cyclic tetrapeptides, that can mainly result in breakthrough in therapy of patients with organ transplants. In addition, they revealed anti-inflammatory, immunosuppressive and skin anticancer activity. Notably, lack of toxicity is observed. The special attention will be given to the survey of non-covalent intermolecular interactions, including comparative analysis with close-related representatives deposited in the structural databases, as well as peptide-mediated protein interactions. The finding can be helpful in further design of more effective innovative peptide-based therapeutics.