Design of short alpha-helical peptides and their activity against pathogenic bacteria Mycobacterium tuberculosis.

The contention of multidrug-resistant bacteria requires the use of new antibiotics. Pandinin 2 (Pin2) is a highly hemolytic antimicrobial peptide that has a central proline residue. Proline forms a structural ‘‘kink’’ linked to its pore-forming activity towards human erythrocytes. In this work, the residue Pro14 of Pin2 was both substituted and flanked by Glycine residues according to the low hemolytic activities of antimicrobial peptides as Magainins and Ponericins, respectively. Both Pin2 variants showed antimicrobial activity against E. coli, S. aureus, and M. tuberculosis. However, Pin2 [GPG] was 30% less hemolytic. To avoid the drawback associated to the cost of synthesis of large peptides, two short peptides were designed and synthesized based on Pin2 [G] and Pin2 [GPG]. Both Pin2 [14] and Pin2 [17] short variants, showed antibiotic activities against E. coli and M. tuberculosis. Besides, Pin2 [14] presented only 25% of hemolysis at 100 μM, while the peptide Pin2 [17] did not show any hemolytic effect at the same concentration. Furthermore, these short antimicrobial peptides showed better activity at molar concentrations against multidrug resistant M. tuberculosis respect to conventional antibiotics. Pin2 [14] and Pin2 [17] have the potential to be used as alternative antibiotics with reduced hemolytic effects.