Structure–Activity Relationship of New Chimeric Analogs of Mastoparan from the Wasp Venom Paravespula lewisii

Abstract

Mastoparan (MP) is an antimicrobial cationic tetradecapeptide with the primary structure INLKALAALAKKIL-NH2. This amphiphilic α-helical peptide was originally isolated from the venom of the wasp Paravespula lewisii. MP shows a variety of biological activities, such as inhibition of the growth of Gram-positive and Gram-negative bacteria, as well as hemolytic activity and activation of mast cell degranulation. Although MP appears to be toxic, studies have shown that its analogs have a potential therapeutic application as antimicrobial, antiviral and antitumor agents. In the present study we have designed and synthesized several new chimeric mastoparan analogs composed of MP and other biologically active peptides such as galanin, RNA III inhibiting peptide (RIP) or carrying benzimidazole derivatives attached to the ε-amino side group of Lys residue. Next, we compared their antimicrobial activity against three reference bacterial strains and conformational changes induced by membrane-mimic environments using circular dichroism (CD) spectroscopy. A comparative analysis of the relationship between the activity of peptides and the structure, as well as the calculated physicochemical parameters was also carried out. As a result of our structure–activity study, we have found two analogs of MP, MP-RIP and RIP-MP, with interesting properties. These two analogs exhibited a relatively high antibacterial activity against S. aureus compared to the other MP analogs, making them a potentially attractive target for further studies. Moreover, a comparative analysis of the relationship between peptide activity and structure, as well as the calculated physicochemical parameters, may provide information that may be useful in the design of new MP analogs.

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“…Jarosław Ruczy ński et al reported that the α-helical structure of a peptide had a significant impact on its interaction with negatively charged membranes. They also found a strong correlation between the helix content of a peptide and antimicrobial activity [26]. This study demonstrated a correlation between the structure of peptides and their biological activity.…”

Antiviral Activities of Mastoparan-L-Derived Peptides against Human Alphaherpesvirus 1

“…To achieve this, the peptide’s secondary structure is an important feature. Numerous reports state mastoparans depend on an α-helix structure to exert their antimicrobial activity [ 60 , 61 ].…”

“…Peptides from the mastoparan family and their analogs can interact with membranes, potentially disrupting bacterial membranes and viral envelopes [ 42 , 60 ]. However, evaluating such activity in a host cell/viral envelope scenario can be challenging, as the lipid composition of host cells and viral membranes is often quite similar.…”

Wasp venom-induced acute kidney injury: current progress and prospects

“…Mastoparan is a 14-amino acid amphiphilic peptide with both hydrophobic and hydrophilic residues that form amphipathic helical structures [ 22 ]. Hydrophobic residues can be embedded into the lipid bilayer of the cell membrane, and hydrophilic residues can form pores on the cell membrane, causing instability of the cell membrane structure and increasing its permeability, thereby leading to cell lysis and inactivation [ 6 , 17 , 23 ].…”

“…Mastoparan has various biological activities; for examples, it can activate guanylate cyclase in addition to G proteins and phospholipases, leading to muscle cell and renal tubular cell lysis [ 6 , 25 ]. In pharmacology, mastoparan is also important owing its antibacterial, antiviral, and antitumor effects [ 20 , 22 ]; however, its application is limited due to its strong hemolytic toxicity and cytotoxicity [ 26 ].…”