mastoparans

Mastoparans are a family of short, cationic, amphipathic peptides found in the venom of wasps, particularly species of the Vespidae family. They are typically 12 to 14 amino acids in length and carry a net positive charge, enabling them to interact strongly with anionic microbial membranes. Most mastoparans adopt an alpha-helical conformation in membrane-like environments, exposing hydrophobic residues on one face to associate with lipid bilayers. A widely cited member, Mastoparan A, has the sequence INLKALAALAKKIL, and many related peptides differ by a few residues but retain the charged, amphipathic character.

Mastoparans exhibit a range of biological activities. They show broad-spectrum antimicrobial activity against bacteria and fungi, largely through disruption of microbial membranes, often via pore formation or carpet-like mechanisms. They can also stimulate degranulation of mast cells and the release of histamine, which is the reason for their name. In cell biology, some mastoparans can activate heterotrimeric G-proteins and influence phospholipase C signaling, making them useful as molecular probes. At higher concentrations they can be cytotoxic to mammalian cells.

Applications and challenges: Because of their membrane-targeting properties, mastoparans are studied as templates for designing novel antimicrobial peptides and as research reagents in signaling studies. Therapeutic development is limited by toxicity to host cells, proteolytic instability, and potential immunogenicity. Researchers pursue sequence modifications, cyclization, d-amino acid substitution, or targeted delivery strategies to improve selectivity and stability.

Taxonomy and diversity: Numerous mastoparan variants have been identified across wasp species, all sharing energetic centers of positive charge and the propensity to form alpha-helices, but with species-specific sequence variation that modulates potency and selectivity.