Anti-Effects of Lipopeptide Derivatives of Lycosin-I.

Abstract

Toxoplasmosis, caused by(), is a serious zoonotic parasitic disease. We previously found that Lycosin-I exhibited anti-activity, but its serum stability was not good enough. In this study, we aimed to improve the stability and activity of Lycosin-I through fatty acid chain modification, so as to find a better anti-drug candidate. The α/ε-amino residues of different lysine residues of Lycosin-I were covalently coupled with lauric acid to obtain eight lipopeptides, namely L-C, L-C-1, L-C-2, L-C-3, L-C-4, L-C-5, L-C-6, and L-C-7. Among these eight lipopeptides, L-Cshowed the best activity againstin vitro in a trypan blue assay. We then conjugated a shorter length fatty chain, aminocaproic acid, at the same modification site of L-C, namely L-an. The anti-effects of Lycosin-I, L-Cand L-an were evaluated via an invasion assay, proliferation assay and plaque assay in vitro. A mouse model acutely infected withtachyzoites was established to evaluate their efficacy in vivo. The serum stability of L-Cand L-an was improved, and they showed comparable or even better activity than Lycosin-I did in inhibiting the invasion and proliferation of tachyzoites. L-an effectively prolonged the survival time of mice acutely infected with. These results suggest that appropriate fatty acid chain modification can improve serum stability and enhance anti-effect of Lycosin-I. The lipopeptide derivatives of Lycosin-I have potential as a novel anti-drug candidate.