Synergistic bactericide and antibiotic effects of dimeric, tetrameric, or palindromic peptides containing the RWQWR motif against Gram-positive and Gram-negative strains.

Dimeric and tetrameric peptides derived from LfcinB (20-25): RRWQWR, LfcinB (20-30): RRWQWRMKKLG, LfcinB (17-31): FKARRWQWRMKKLGA, or the palindromic sequence LfcinB (21-25): RWQWRWQWR were obtained by means of the SPPS-Fmoc/Bu methodology. The antibacterial activity of these molecules was evaluated against (ATCC 25922 and ATCC 11775), (ATCC 25923), (ATCC 29212), and (ATCC 27853). The dimer LfcinB (20-25): (RRWQWR)K-Ahx, the tetramer LfcinB (20-25): (RRWQWR)K-Ahx-C, and the palindromic sequence LfcinB (21-25) exhibited the highest antibacterial activity against the tested bacterial strains. In all cases, the antibacterial activity was dependent on peptide concentration. The polyvalent molecules LfcinB (20-25) and LfcinB (20-25) exhibited bacteriostatic and bactericidal activity against , , and strains; additionally, this dimer and this tetramer combined with ciprofloxacin exhibited a synergistic antibacterial effect against ATCC 25922 and , respectively. Furthermore, the peptides LfcinB (20-30), LfcinB (20-25), and LfcinB (21-25) combined with vancomycin exhibited a synergistic antibacterial effect against and , respectively. This study showed that polyvalent peptides derived from LfcinB exhibit significant antibacterial activity, suggesting that these peptides could have a therapeutic application. Furthermore, our results suggest that polyvalent peptide synthesis could be considered as an innovative and viable strategy for obtaining promising antimicrobial molecules.