Meucin-25

Background: Scorpion venom is the most expensive and deadly venom with exciting medical prospects and having a potential as a source of drug candidates. A number of scorpion venom peptides have shown promising site specificity and are involved in the regulation of biological mechanisms. Due to the structural and functional specificity, the scorpion peptides are widely used for the development of specific drugs especially for the cardiovascular and other immune diseases. In this review, we summarize scorpion venom's biological activities such as antimicrobial, antiviral, anti-cancerous and in immune diseases. Evolutionary perspective of peptides derived from different scorpion venoms are also described in this review. The most significant venom peptides are; Ctriporin, Chlorotoxins (cltx), Neopladine I and II, Meucin 24, Meucin 25 and Hp 1090. The most recognized scorpion species with pharmaceutical activities are; Pandinus imperator, Chaerilustricostatus, Buthus martensii, Mesobuthus eupeus, Leiurus quinnquestriatus, Tityus discrepans and Heterometrus bengalensis. Conclusion: The role of peptides in cardiovascular events and in treating osteoporosis signifies their importance. The role of peptides against pathogens, skin infections, pain-relieving effects, anti-malarial and anti-viral effects are discussed in detail. We further, summarized the classification of scorpion peptides among different toxins, their evolutionary process and the pattern of scorpion venom resource analysis.

Plasmodium falciparum is a pathogen of human malaria which causes millions of deaths per year due to the ever-increasing drug resistance by the parasite, and thus novel antimalarial agents are urgently needed. In this work, we report two cDNA clones from the scorpion Mesobuthus eupeus venom gland, which encode peptides inhibiting the development of Plasmodium berghei, killing intraerythrocytic P. falciparum, and toxic to the Drosophila S2 cell at micromolar concentrations. One peptide of 24 amino acids (named meucin-24) shares high sequence identity to the amino-terminus of a family of scorpion venom long-chain K(+) channel toxins (LcKTx) and two frog antimicrobial peptides (magainin1 and 2). Sequencing genomic DNA of meucin-24 identified this short peptide as a product of a putative guanine-to-adenine RNA editing from a M. eupeus LcKTx transcript. Another peptide, named meucin-25, contains 25 residues and does not share sequence similarity with any known peptides. Circular dichroism analysis of chemically synthesized peptides demonstrates that meucin-24 presents an essential random coil conformation in water, but its alpha-helical content largely increases in the presence of 50% trifluoroethanol, a membrane-mimicking environment. This finding was further verified by its NMR structure that showed an alpha-helical amphipathic architecture in the region of residues 4-20. CD results indicate that meucin-25 mainly adopts a beta-sheet structure in water but TFE promotes its alpha-helical formation, suggesting its conformational flexibility. Killing of intraerythrocytic P. falciparum without harming mammalian cells (erythrocytes and GC-2 cell) make them attractive candidates for antimalarial drug design.

Background: Scorpion venom glands produce some antimicrobial peptides (AMP) that can rapidly kill a broad range of microbes and have additional activities that impact on the quality and effectiveness of innate responses and inflammation. Objectives: In this study, we reported the identification of a cDNA sequence encoding cysteine-free antimicrobial peptides isolated from venomous glands of this species. Materials and methods: Total RNA was extracted from the Iranian mesobuthus eupeus venom glands, and cDNA was synthesized by using the modified oligo (dT). The cDNA was used as the template for applying Semi-nested RT- PCR technique. PCR Products were used for direct nucleotide sequencing and the results were compared with Gen Bank database. Results: A 213 BP cDNA fragment encoding the entire coding region of an antimicrobial toxin from the Iranian scorpion M. Eupeus venom glands were isolated. The full-length sequence of the coding region was 210 BP contained an open reading frame of 70 amino with a predicted molecular mass of 7970.48 Da and theoretical Pi of 9.10. The open reading frame consists of 210 BP encoding a precursor of 70 amino acid residues, including a signal peptide of 23 residues a propertied of 7 residues, and a mature peptide of 34 residues with no disulfide bridge. The peptide has detectable sequence identity to the Lesser Asian mesobuthus eupeus MeVAMP-2 (98%), MeVAMP-9 (60%) and several previously described AMPs from other scorpion venoms including mesobuthus martensii (94%) and buthus occitanus Israelis (82%). Conclusions: The secondary structure of the peptide mainly consisted of α-helical structure which was generally conserved by previously reported scorpion counterparts. The phylogenetic analysis showed that the Iranian MeAMP-like toxin was similar but not identical with that of venom antimicrobial peptides from lesser Asian scorpion mesobuthus eupeus.