Lactoferricin

LfcinB disrupts bacterial membranes through its cationic tryptophan-rich core. Tryptophan residues insert into the hydrophobic core of membranes through aromatic-lipid interactions, while arginine residues provide electrostatic targeting. The combination of electrostatic attraction and hydrophobic anchoring creates a highly effective membrane-disrupting unit. LPS binding in Gram-negatives is mediated by the arginine-rich face, triggering outer membrane permeabilization before inner membrane disruption.

LfcinB induces apoptosis in multiple cancer cell lines at concentrations that spare normal cells. The cancer cell selectivity is attributed to anionic phosphatidylserine exposure on cancer cell surfaces. In Jurkat leukemia cells, LfcinB activates caspase-3 through mitochondrial membrane disruption. Additionally, LfcinB inhibits VEGF-induced angiogenesis by binding to VEGF and heparan sulfate proteoglycans, potentially contributing to anti-tumor effects through anti-angiogenic mechanisms.

LfcinB shows activity against E. coli, P. aeruginosa, S. aureus (including MRSA), C. albicans, and HSV-1/HSV-2. MIC values of 1-10 ug/mL are typical against susceptible strains. Food-grade applications have been explored for natural preservation of dairy and meat products. The peptide retains activity in the presence of moderate salt concentrations relevant to food matrices, unlike many synthetic AMPs.

LfcinB and its synthetic derivatives show selective cytotoxicity against Jurkat leukemia cells, fibrosarcoma, neuroblastoma, and colon cancer cell lines. The minimal active sequence for anticancer activity is the WRWYCR hexapeptide which can be synthetically produced. Anti-angiogenic effects at sub-cytotoxic concentrations (1-5 uM) contribute to potential in vivo anti-tumor activity.