Antimicrobial Peptide Arenicin-1 Derivative Ar-1-(C/A) as Complement System Modulator

Abstract

Antimicrobial peptides (AMPs) are not only cytotoxic towards host pathogens or cancer cells but also are able to act as immunomodulators. It was shown that some human and non-human AMPs can interact with complement proteins and thereby modulate complement activity. Thus, AMPs could be considered as the base for complement-targeted therapeutics development. Arenicins from the sea polychaete Arenicola marina, the classical example of peptides with a β-hairpin structure stabilized by a disulfide bond, were shown earlier to be among the most prospective regulators. Here, we investigate the link between arenicins’ structure and their antimicrobial, hemolytic and complement-modulating activities using the derivative Ar-1-(C/A) without a disulfide bond. Despite the absence of this bond, the peptide retains all important functional activities and also appears less hemolytic in comparison with the natural forms. These findings could help to investigate new complement drugs for regulation using arenicin derivatives.

Novel β-Hairpin Peptide from Marine Polychaeta with a High Efficacy against Gram-Negative Pathogens

“…In this regard, the family of β-hairpin peptides termed arenicins—isolated from coelomocytes of marine polychaeta Arenicola marina —attracts much attention. There are three members of this family: arenicin-1, -2 containing one disulfide bridge and arenicin-3 with two disulfide bonds [ 3 , 4 , 5 , 6 ]. Natural isoforms of arenicins exhibit a pronounced antimicrobial activity against Gram-negative and Gram-positive bacteria as well as towards yeasts and pathogenic fungi.…”

Immunomodulatory and Allergenic Properties of Antimicrobial Peptides

“…The authors of this study discuss the possibility of interaction of AMPs with complement proteins, C1q and C3, and the regulation of their functional activity [ 158 ]. The influence of structural changes in arenicins on their interaction with complement proteins and biological activity was studied [ 159 ]. The arenicin-1 derivative without a disulfide bond (Ar-1- (C/A)), despite the absence of this bond, retains all important functional activities and also exhibits lower toxicity compared to the natural analogs previously discovered [ 160 , 161 , 162 ].…”

Marine Peptides: Structure, Bioactivities, and a New Hope for Therapeutic Application

“…Earlier, structure-function relationships of arenicins have been extensively investigated [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Arenicin was shown to modulate the human complement system [ 26 ]. Here, the authors reported the property change in arenicin-1 derivative Ar-1-(C/A) structure and its antimicrobial, hemolytic and complement-modulating activities in comparison with those of the natural peptide.…”

“…Here, the authors reported the property change in arenicin-1 derivative Ar-1-(C/A) structure and its antimicrobial, hemolytic and complement-modulating activities in comparison with those of the natural peptide. Despite the absence of a disulfide bond, the peptide possessed all important functional features, but its hemolytic activity reduced [ 26 ]. The use of marine peptides as new complement modulators has several advantages.…”

“…They do not resemble human peptides, which allows to avoid cross-reactivity and side effects. Besides, this approach promotes antimicrobial effects, taking into account the inhibited complement system [ 26 ]. In this Special Issue, a novel BRICHOS-domain related AMP from the marine polychaeta Capitella teleta , named capitellacin, was reported [ 17 ].…”