Abstract
Plants are extensively used in traditional medicine, and several plant antimicrobial peptides have been described as potential alternatives to conventional antibiotics. However, after more than four decades of research no plant antimicrobial peptide is currently used for treating bacterial infections, due to their length, post-translational modifications or high dose requirement for a therapeutic effect . Here we report the design of antimicrobial peptides derived from a guava glycine-rich peptide using a genetic algorithm. This approach yields guavanin peptides, arginine-rich α-helical peptides that possess an unusual hydrophobic counterpart mainly composed of tyrosine residues. Guavanin 2 is characterized as a prototype peptide in terms of structure and activity. Nuclear magnetic resonance analysis indicates that the peptide adopts an α-helical structure in hydrophobic environments. Guavanin 2 is bactericidal at low concentrations, causing membrane disruption and triggering hyperpolarization. This computational approach for the exploration of natural products could be used to design effective peptide antibiotics.
Highlights
Plants are extensively used in traditional medicine, and several plant antimicrobial peptides have been described as potential alternatives to conventional antibiotics
The ratio between hydrophobic moment and α-helix propensity was used in the fitness function for selecting amphipathic α-helical peptides, while the initial population consisted of four Pg-AMP1 fragments derived according to specific physicochemical properties (Fig. 1a)
The amino acid composition of all the guavanins was different from other antimicrobial peptides (AMPs) deposited in the Antimicrobial Peptides Database (APD), even taking into account only those peptides assigned with an α-helical structure (Fig. 1d), and despite guavanins are Arg-rich peptides, it draws attention the fact that they use Tyr residues as the hydrophobic counterpart (Fig. 1e)
Summary
Plants are extensively used in traditional medicine, and several plant antimicrobial peptides have been described as potential alternatives to conventional antibiotics. We report the design of antimicrobial peptides derived from a guava glycine-rich peptide using a genetic algorithm This approach yields guavanin peptides, arginine-rich α-helical peptides that possess an unusual hydrophobic counterpart mainly composed of tyrosine residues. Guavanin 2 is bactericidal at low concentrations, causing membrane disruption and triggering hyperpolarization This computational approach for the exploration of natural products could be used to design effective peptide antibiotics. Infections caused by Gram-negative bacteria have been associated with more than 60% of pneumonia cases and more than 70% of urinary tract infections in intensive care units[2] Such bacteria are highly efficient in generating mutants and sharing genes that encode for mechanisms of antibiotic resistance[1]. It is possible to identify in nature, mainly in plants, various AMPs with distinct composition, including glycine-rich Pg-AMP120, glycine- and histidine-rich shepherin I and II21 or proline-rich BnPRP122, representing other parcels of the combinatorial space
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