Antimicrobial/cytolytic peptides from the venom of the North African scorpion, Androctonus amoreuxi: biochemical and functional characterization of natural peptides and a single site-substituted analog.

Abstract

The venoms of scorpions are complex cocktails of polypeptide toxins that fall into two structural categories: those that contain cysteinyl residues with associated disulfide bridges and those that do not. As the majority of lethal toxins acting upon ion channels fall into the first category, most research has been focused there. Here we report the identification and structural characterization of two novel 18-mer antimicrobial peptides from the venom of the North African scorpion, Androctonus amoreuxi. Named AamAP1 and AamAP2, both peptides are C-terminally amidated and differ in primary structure at just two sites: Leu-->Pro at position 2 and Phe-->Ile at position 17. Synthetic replicates of both peptides exhibited a broad-spectrum of antimicrobial activity against a Gram-positive bacterium (Staphylococcus aureus), a Gram-negative bacterium (Escherichia coli) and a yeast (Candida albicans), at concentrations ranging between 20 μM and 150 μM. In this concentration range, both peptides produced significant degrees of hemolysis. A synthetic replicate of AamAP1 containing a single substitution (His-->Lys) at position 8, generated a peptide (AamAP-S1) with enhanced antimicrobial potency (3-5 μM) against the three test organisms and within this concentration range, hemolytic effects were negligible. In addition, this His-->Lys variant exhibited potent growth inhibitory activity (ID(50) 25-40 μm) against several human cancer cell lines and endothelial cells that was absent in both natural peptides. Natural bioactive peptide libraries, such as those that occur in scorpion venoms, thus constitute a unique source of novel lead compounds with drug development potential whose biological properties can be readily manipulated by simple synthetic chemical means.

• Authors: Ammar Almaaytah, Mei Zhou, Lei Wang, Tianbao Chen, Brian Walker, Chris Shaw
• Journal: Peptides (Peptides) Vol. 35 Issue 2 Pg. 291-9 (Jun 2012) ISSN: 1873-5169 [Electronic] United States
• PMID: 22484288 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Infective Agents
• Antifungal Agents
• Antimicrobial Cationic Peptides
• Peptides
• Scorpion Venoms

Topics

• Amino Acid Sequence
• Amino Acid Substitution
• Animals
• Anti-Infective Agents (chemistry, isolation & purification, pharmacology)
• Antifungal Agents (chemistry, isolation & purification, pharmacology)
• Antimicrobial Cationic Peptides (chemistry, isolation & purification, pharmacology)
• Base Sequence
• Candida albicans (drug effects)
• Cell Line, Tumor (drug effects)
• Cell Proliferation (drug effects)
• Endothelial Cells (drug effects)
• Escherichia coli (drug effects)
• Humans
• Male
• Microbial Sensitivity Tests
• Peptides (chemistry, isolation & purification, pharmacology)
• Scorpion Venoms (chemistry, isolation & purification)
• Scorpions (metabolism)
• Staphylococcus aureus (drug effects)