The ATPase activity of the mycobacterial plasma membrane is inhibited by the LL37-analogous peptide LLAP
Publication date: Available online 26 July 2015 Source:Peptides Author(s): Sandra Chingaté, Gabriela Delgado, Luz Mary Salazara, Carlos-Yesid Soto The emergence of multidrug-resistant Mycobacterium tuberculosis strains has led to the development of new antituberculous agents. In this context, antimicrobial targeting proteins to the cell membrane are interesting due to the avoidance of the plasma membrane permeation. Through this study, the antimicrobial activity, cellular toxicity, as well as the effect on the mycobacterial cell membrane ATPase activity of a cathelicidin-analogous peptide were assessed. By using bioinformatics analyses, a 15 amino acid LL37-analogous peptide called LLAP, which has the amino acid sequence: GRKSAKKIGKRAKRI, was designed to improve its helical structure and antibacterial activity compared to the native sequence. The LLAP peptide was synthesized, purified by RP-HPLC and its structural characteristics were determined by MALDI-TOF MS and circular dichroism. Compared to the native amino acid sequence, the minimum inhibitory concentration and cytotoxic activity of LLAP were 4.0 and 5.6-fold lower, respectively. In addition, the hemolytic activity of LLAP was lower than 1.1% and the cytotoxic activity of peptides was similar for both peptides. Interestingly, the LLAP peptide displayed approximately 50% inhibition of basal ATPase activity of the mycobacterial plasma membrane, which could in turn be associated with the impaired cell viabili...
Source: Peptides - Category: Biochemistry Source Type: research