Brevinin

Brevinins adopt an amphipathic alpha-helical conformation upon membrane contact. The N-terminal helix interacts with bacterial phospholipids while the C-terminal Rana box (disulfide-cyclized ring) anchors to the membrane. Brevinin-1 shows primarily membranolytic activity, while Brevinin-2 analogs can partially penetrate into the membrane to create toroidal pores. The cyclic Rana box also contributes to proteolytic stability.

Brevinin-2ERb selectively kills NSCLC H322 cells at concentrations that spare normal human bronchial epithelial cells. The selectivity is attributed to differences in surface phosphatidylserine exposure and membrane fluidity between cancer and normal cells. Apoptotic pathways including mitochondrial membrane disruption have been documented, suggesting both direct lysis and triggered apoptosis contribute to cancer cell killing.

Brevinin-2ERb and modified analogs demonstrate selective killing of NSCLC cell lines with IC50 values of 10-30 uM while sparing normal bronchial epithelium. The peptide induces apoptosis through mitochondrial pathway activation. Structure-activity studies have identified modifications that improve cancer cell selectivity and reduce hemolytic activity, making this scaffold a lead for anticancer AMP development.

Brevinin-2 fragments have been identified as potent stimulators of insulin release from pancreatic beta cells. Sub-nanomolar concentrations of specific brevinin analogs stimulate glucose-dependent insulin secretion without causing direct toxicity to beta cells. This insulinotropic activity is distinct from the antimicrobial mechanism and represents a separate therapeutic potential for type 2 diabetes.