Amino acid substitutions in an alpha-helical antimicrobial arachnid peptide affect its chemical properties and biological activity towards pathogenic bacteria but improves its therapeutic index
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Four variants of the highly hemolytic antimicrobial peptide Pin2 were chemically synthesized with the aim to investigate the role of the proline residue in this peptide, by replacing it with the motif glycine-valine-glycine [GVG], which was found to confer low hemolytic activity in a spider antimicrobial peptide. The proline residue in position 14 of Pin2 was substituted by [V], [GV], [VG] and [GVG]. Only the peptide variant with the proline substituted for [GVG] was less hemolytic compared to that of all other variants. The peptide variant [GVG] kept its antimicrobial activity in Muller–Hilton agar diffusion assays, whereas the other three variants were less effective. However, all Pin2 antimicrobial peptide variants, were active when challenged against a Gram-positive bacteria in Muller–Hilton broth assays suggesting that chemical properties of the antimicrobial peptides such as hydrophobicity is an important indication for antimicrobial activity in semi-solid environments.
KeywordsAntimicrobial peptide Arachnid, pandinin 2 Peptide synthesis S. aureus
Minimum inhibitory concentration
This work was supported by grants from CONACyT 83962/2007 to E.V., and CONACyT 49773/24968 to G.C. The mass spectrometry determination conducted by Dr. Fernando Zamudio is greatly acknowledged. The authors also acknowledge QBP Ma. Rocio Patiño Maya from Instituto de Química–UNAM for CD spectra data acquisition. Alexis Rodriguez is recipient of a PhD scholarship (#199738) from CONACyT.
Conflict of interest statement
The authors declare that they have no conflict of interest.
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