In silico modificiton of Cathelicidins generates analogous peptides with improved antimycobacterial activity

Abstract

Tuberculosis is a bacterial infection that annually produces approximately 1.3 million of deaths around the world; this infectious disease has become an important public health problem due to the emergence of multidrug-resistant Mycobacterium tuberculosis strains. In this study, bioinformatics tools were used to design 15 aminoacid analogous sequences from the cathelicidin LL37, CAP 18 and PMAP 36 that in silico displayed improved helical structure and antibacterial activity in comparison to the native sequences. The analogous and native aminoacid sequences were synthesized using the Fmoc strategy, purified by RP-HPLC and characterized by MALDITOF and circular dichroism. According to an in vitro assay of viability on M. smegmatis mc2155 cells, an analogous peptide from CAP-18 displayed a minimal inhibitory concentration 10-fold lower that the showed for the native aminoacid sequence. In addition, the designed analogous peptides showed human erythrocytes hemolysis lesser than 10% and significant inhibition of the basal ATPase activity of mycobacterial plasma membrane vesicles. The results obtained suggest that the designed peptides diminish the mycobacterial viability and could be useful as antituberculous compounds. © Springer International Publishing Switzerland 2014.