Mediterranean Biochemical Network

Study on the properties of bio-active peptides from marine molluscs

This project involves the University of Roma III (P. Ascenzi) Genova (M. Bolognesi) and Ferrara (E. Menegatti).
It is financially supported by a grant from the Ministero dei Beni Culturali of Italy, through the International Malacology Association (AMI, Rome). The research is aimed to identify and characterize biotechnologically and therapeutically relevant proteins extracted chiefly from marine molluscs. In particular, this research has presently focused on conopeptides, the bio-active components of the venom from the molluscan genus Conus.
This large and diverse genus of prosobranch gastropods which includes more than 500 species widespread in all tropical and subtropical marine regions is a major component of shallow coral reef- associated communities. In the temperate Mediterranean sea, a single species is recognized, Conus ventricosus, whose venom is presently under study.

Several and diverse peptides contained, as a specific, distinct complement among other compounds in the venom of Conus, have been optimized through evolution to target specific ion channel and membrane receptors, with very high affinity and selectivities. The majority of these peptides are short aminoacid chains, either linear or disulphide bridged, consisting of 8 to 30 aminoacidic residues. Some of them, classified as conotoxins, are already employed as a useful tool as highly specific probes for neuronal and muscolar ion- channel subunities. Researchers are now exploiting the potential therapeutic value. Possible applications have been already pointed out. The w-conotoxins, for instance, targeting Calcium channels, proved to be efficient in pain therapy and stroke. The a-conotoxins, which antagonize the nicotinic acetylcoline receptor, appear to have potential application in anxiety, Parkinson’s disease, cancer, hyperthension, and pain.

The k-conotoxins targeting the Potassium channels, have a potential use in the therapy of hypertension, arrhitmya and ashma. Conantokins, originally isolated from the venom of fishing- hunting cone snails, are 17 aminoacid linear peptides that adopt an a- helical conformation in solution and contain post traslational modifications including five carboxy- glutamic acid residues and an amidated C-terminal. Conantokins have proved to act on the N-Methyl-D-Aspartate receptor (NMDA) thus promising useful applications in epilepsy, Parkinson’s disease and stroke. Contulakins, targeting the neurotensin receptor may be employed in the therapy of pain and disorders of the central nervous system (CNS).
Thus, the high affinity and specificity, joining the minimum molecular weight are a unique characteristic of conopeptides, allowing an easy synthesis and enabling drugs engineering. As different species of Conus are investigated, new effects and different properties are observe opening new insights in pharmaceutical perspectives.

Universities involved in this project:

University of Roma - Italy

Prof. Paolo Ascenzi (Roma III)

University of Genova - Italy

Prof. M. Bolognesi

University of Ferrara - Italy

Prof. E. Menegatti

Ministero dei Beni Culturali of Italy

International Malacology Association (AMI Roma, Italy)