Defensin
A class of small, cysteine-rich antimicrobial peptides produced naturally by humans as part of the innate immune system. Defensins kill bacteria, fungi, and viruses by disrupting their cell membranes. They represent a natural model for the development of peptide-based antimicrobial drugs.
Technical Context
Human defensins: alpha-defensins (HNP-1 through HNP-4, found in neutrophil granules; HD-5, HD-6, found in Paneth cells of the small intestine) and beta-defensins (HBD-1 through HBD-4, expressed by epithelial cells of skin, airways, and urogenital tract). Structure: 18-45 amino acids with 6 conserved cysteines forming 3 disulphide bonds in a characteristic beta-sheet scaffold. Mechanism: electrostatic attraction to negatively charged bacterial membranes (microbial membranes have more anionic phospholipids than human cell membranes), followed by membrane disruption through pore formation or carpet model. Defensins also modulate adaptive immunity — chemotactic for dendritic cells and T cells, linking innate and adaptive responses. Therapeutic defensin development faces challenges: production cost (multiple disulphide bonds complicate synthesis), potential cytotoxicity at antimicrobial concentrations, and salt sensitivity.