Influence of N‐terminus modifications on the biological activity, membrane interaction, and secondary structure of the antimicrobial peptide hylin‐a1

Abstract

Recently the peptide Hy-a1 (IFGAILPLALGALKNLIK), with antimicrobial activity, was isolated from the skin secretion of the frog Hypsiboas albopunctatus. The aim of the present work was to evaluate four analogues with introduction of acetyl group, Asp or Lys at the N-terminus of antimicrobial peptide Hy-al to supply information about the relationship of structure-biological activity. The antimicrobial activities were assayed by measuring growth inhibition of four species of bacteria and four species of fungus. The hemolytic activity was also tested. The peptide containing Trp instead of Leu in position 6 (for fluorescence studies) presented MIC values comparable to wild type sequence: 32 μmol L(-1) , 32 μmol L(-1) , 8 μmol L(-1) , and 2 μmol L(-1) for E. coli, P. aeruginosa, S. aureus, and B. subtilis, respectively. Two peptides with this modification and containing one acetyl group or Asp residue at the N-terminal region showed activities only against Gram-positive bacteria. Different results were observed when the residue added was Lys. In this case, the activity against the microorganisms was sustained or increased. Conformational properties were investigated by CD techniques in water, TFE, and in zwitterionic micelles (LPC). The CD experiments demonstrated that, in water, the peptides had a random structure, but in TFE and LPC solutions they acquired an ordered structure, composed mainly by α-helix. However, these data have no relationship with activity against Gram-positive bacteria. These results showed that the N-terminal region of the peptide Hy-a1 has key roles in its antibacterial action toward different types of bacteria.

Deconstructing the DGAT1 enzyme: Binding sites and substrate interactions

“…3E, G, H) were in agreement with them being in a disordered state, with the Trp residues exposed to the solvent, producing a maximum fluorescence emission (λ max ) centered at 355 nm [27][28][29].…”

Surface Physical Activity and Hydrophobicity of Designed Helical Peptide Amphiphiles Control Their Bioactivity and Cell Selectivity

“…15 Additionally, simple terminal modifications including N-terminal acetylation, C-terminal amidation, end-tagging and single amino acid substitutions have also been employed to alter the properties of AMPs and ACPs, with some of these peptide variants showing enhanced antibacterial and anticancer activity and cell selectivity. [16][17][18] Furthermore, previous studies have also suggested that end capping and cyclization of hexameric peptide sequences of RRWQWR and RRWWRF or end-tagging of short peptides KNK10 (KNKGKKNGKH) and GKH17…”

Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha

“…Thus, selected strategies have been performed to improve peptide stability, efficacy, delivery, and selectivity (10,21,27,32,34,38,45). As the plasma membrane is the target for cAMPs, selectivity is important and is responsible for their cytotoxicity to human cells.…”

“…It has been determined that high helicity, hydrophobicity, and amphipathicity are correlated with an increase in eukaryotic cell toxicity (5). We have also shown that the N-terminal region is important for the hemolytic activity of synthetic peptides containing sequences from the N termini of sticholysins (7) and for selectivity of the cAMPs (10). Therefore, efforts have been undertaken to improve the selectivity of cAMPs, including sequence modification to optimize their physicochemical parameters (18,27,38,43).…”