Abstract
Antimicrobial peptides are an important class of therapeutic agent used against a wide range of pathogens such as Gram-negative and Gram-positive bacteria, fungi, and viruses. Mastoparan (MpVT) is an α-helix and amphipathic tetradecapeptide obtained from Vespa tropica venom. This peptide exhibits antibacterial activity. In this work, we investigate the effect of amino acid substitutions and deletion of the first three C-terminal residues on the structure–activity relationship. In this in silico study, the predicted structure of MpVT and its analog have characteristic features of linear cationic peptides rich in hydrophobic and basic amino acids without disulfide bonds. The secondary structure and the biological activity of six designed analogs are studied. The biological activity assays show that the substitution of phenylalanine (MpVT1) results in a higher antibacterial activity than that of MpVT without increasing toxicity. The analogs with the first three deleted C-terminal residues showed decreased antibacterial and hemolytic activity. The CD (circular dichroism) spectra of these peptides show a high content α-helical conformation in the presence of 40% 2,2,2-trifluoroethanol (TFE). In conclusion, the first three C-terminal deletions reduced the length of the α-helix, explaining the decreased biological activity. MpVTs show that the hemolytic activity of mastoparan is correlated to mean hydrophobicity and mean hydrophobic moment. The position and spatial arrangement of specific hydrophobic residues on the non-polar face of α-helical AMPs may be crucial for the interaction of AMPs with cell membranes.
Highlights
Introduction published maps and institutional affilIn recent years, the development of multidrug-resistant bacteria, in particular in hospital patients, has led to an increased interest in the search for new antibiotics [1]
In the Antimicrobial Peptide Database (APD), 14% of the antimicrobial peptides known to date adopt an α-helix structure [5]
Soluble V. tropica crude venom was fractionated by reverse-phase high-performance liquid chromatography (HPLC), and the antimicrobial activity of the fractions was investigated
Summary
The development of multidrug-resistant bacteria, in particular in hospital patients, has led to an increased interest in the search for new antibiotics [1]. The search for new antibiotic substances found an almost inexhaustible source of potential therapeutic agents amongst antimicrobial peptides (AMPs), with sources including bacteria, archaea, protists, fungi, animal venom, and plants [2,3]. AMPs are usually small (lower than 100 amino acids), charged, amphipathic molecules found as components of an organism’s innate immune system, and have a broad-spectrum antimicrobial activity or are involved in immune regulation, wound healing, or apoptosis. AMPs can resemble a wide variety of structures but typically have an excess positive charge of +2 to +9, around 50% hydrophobicity, and the acquisition of a different secondary structure in membranous environments [4].
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