Latarcins: Antimicrobial and cell-penetrating peptides from spider venom.

Abstract

The venom of the ant spider Lachesena tarabaevi is reported to be rich in linear membrane active peptides[1]. Latarcins is a group of seven linear antimicrobial peptides found in the venom of this spider. We have recently studied this entire group of peptides to address the secondary state, membrane orientation and toxicity using circular dichroism (CD) spectroscopy, oriented CD (OCD), solid-state 31P-/15N-NMR and fluorescence spectroscopy[2]. Our results show that all peptides fold into an α-helical state in presence of lipids. OCD and NMR experiments show that these helices are either surface bound, tilted in the membrane or tend to aggregate in the lipid bilayer. The most tilted peptide, Ltc2a, shows indiscriminate membrane-toxicity and damages natural membranes (antimicrobial and hemolytic activity) as well as artificial membranes (vesicle leakage) where as the aggregating peptide, Ltc6a, shows no toxicity towards natural membranes but instead induces leakage of artificial lipid vesicles. Other latarcins (Ltc1, Ltc3a, Ltc4a and Ltc5a) show high activity and are selective in bacterial killing without causing bilayer disturbances. This result indicates that latarcins may have intracellular targets, and thus the ability of these peptides to enter cancer cells was also studied. In order to reduce the membrane toxicity, truncated latarcins (short latarcins, Sltc) were synthesized. Shorter latarcins turned out to be even less cytotoxic and highly cell-penetrating. These biophysical studies of latarcins and their shorter analogues on model membranes along with their influence on natural membranes will be presented.