Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 72, Issue 23, Pages 4501-4522Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-015-2016-x
Keywords
Biologically active compounds; Mechanism of action; Cytolytic toxin; Correlation analysis; Antimicrobial peptide; Structure-function relationship
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Funding
- Russian Foundation for Basic Research [13-04-02128, 13-04-00825]
- Program Molecular and Cellular Biology of the Russian Academy of Sciences
- Russian Federation [NSh-1924.2014.4]
- Russian Science Foundation [14-24-00118]
- Russian Science Foundation [14-24-00118] Funding Source: Russian Science Foundation
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Arthropod venoms feature the presence of cytolytic peptides believed to act synergetically with neurotoxins to paralyze prey or deter aggressors. Many of them are linear, i.e., lack disulfide bonds. When isolated from the venom, or obtained by other means, these peptides exhibit common properties. They are cationic; being mostly disordered in aqueous solution, assume amphiphilic alpha-helical structure in contact with lipid membranes; and exhibit general cytotoxicity, including antifungal, antimicrobial, hemolytic, and anticancer activities. To suit the pharmacological needs, the activity spectrum of these peptides should be modified by rational engineering. As an example, we provide a detailed review on latarcins (Ltc), linear cytolytic peptides from Lachesana tarabaevi spider venom. Diverse experimental and computational techniques were used to investigate the spatial structure of Ltc in membrane-mimicking environments and their effects on model lipid bilayers. The antibacterial activity of Ltc was studied against a panel of Gram-negative and Gram-positive bacteria. In addition, the action of Ltc on erythrocytes and cancer cells was investigated in detail with confocal laser scanning microscopy. In the present review, we give a critical account of the progress in the research of Ltc. We explore the relationship between Ltc structure and their biological activity and derive molecular characteristics, which can be used for optimization of other linear peptides. Current applications of Ltc and prospective use of similar membrane-active peptides are outlined.
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