State of the Art in the Studies on Crotamine, a Cell Penetrating Peptide from South American Rattlesnake

Abstract

Animal venoms comprise a naturally selected cocktail of bioactive peptides/proteins and other molecules, each of which playing a defined role thanks to the highly specific interactions with diverse molecular targets found in the prey. Research focused on isolation, structural, and functional characterizations of novel natural biologics (bioactive peptides/proteins from natural sources) has a long way to go through from the basic science to clinical applications. Herein, we overview the structural and functional characteristics of the myoneurotoxin crotamine, firstly isolated from the South American rattlesnake venom. Crotamine is the first venom peptide classified as a natural cell penetrating and antimicrobial peptide (CPP and AMP) with a more pronounced antifungal activity. In contrast to other known natural CPPs and AMPs, crotamine demonstrates a wide spectrum of biological activities with potential biotechnological and therapeutic values. More recent studies have demonstrated the selective in vitro anticancer activity of crotamine. In vivo, using a murine melanoma model, it was shown that crotamine delays tumor implantation, inhibits tumor cells proliferation, and also increases the survival of mice engrafted with subcutaneous melanoma. The structural and functional properties and also the possible biotechnological applications of minimized molecules derived from crotamine are also discussed.

Anticancer potential of bioactive peptides from animal sources

“…Most venoms are a complex mixture of several proteins, peptides, enzymes, toxins and non-protein components. Bioactive peptides from snake venoms have significantly contributed to the treatment of many medical conditions, and some peptides and enzymes from snake venom may specifically target cancer cell membranes, affecting the migration and proliferation of these cells (157,158).…”

Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs

“…Crotamine is a 42-aa neuro-and myotoxic peptide, initially isolated from the South American rattlesnake (C. durissus terrificus). Crotamine's anti-infective, antitumoral, and cell-penetrating properties have been deeply characterized both in vitro and in vivo [144]. Crotamine displays modest antibacterial activity (MICs in the 25-100 µg/mL range against E. coli strains) and does not induce hemolysis at high concentrations (no hemolysis observed up to 1024 µg/mL) [145].…”

New generation CPPs show distinct selectivity for cancer and noncancer cells

“…Mini-maurocalcine is prone to proteolytic degradation, whereas D-maurocalcine, an analog with all amino acids in the D-configuration, conveys more efficient cell penetration and proteolytic stability. 50 Hence, the underlying Cys (DY676)-[4-Ser-crotamine(Δ10-37)] could be used for further studies on the identification of heterogenic cancer subpopulations within different neoplasia. However, the strong fluorescence was confined to a few cells spotted within clusters of less fluorescing or nonfluorescing breast cancer cells (Supporting Information Figure S6).…”