Alpha-defensin peptide (None standardized for the family; individual peptides have common abbreviations such as HNP-1, HNP-2, HNP-3 (Human Neutrophil Peptides), HD5, HD6 (Human Defensin 5 and 6))

Alpha-defensin peptides are a subclass of defensins, small cationic peptides (18–45 amino acids; 2–6 kDa), characterized by six conserved cysteines forming three intramolecular disulfide bonds and a beta-sheet-rich amphipathic structure. They are mainly found in mammalian leukocytes (neutrophils) and intestinal Paneth cells, mediating broad-spectrum antimicrobial and immunomodulatory actions. Alpha-defensins can directly disrupt microbial membranes and neutralize toxins, while also modulating immune responses, including chemotaxis, cytokine release, and regulation of cell death. Altered expression is associated with disease pathology in infections, inflammation, cancer, and autoimmune conditions. Alpha-defensins and their synthetic mimetics (such as brilacidin) are being developed as novel antibiotics, and alpha-defensin levels are under investigation as clinical biomarkers for disease risk and activity. Therapeutic development faces challenges due to the complex and sometimes double-edged role of defensins in human health.

Other names

Human neutrophil peptide 1, 2, 3, 4 (HNP-1, HNP-2, HNP-3, HNP-4)Human defensin 5, 6 (HD5, HD6)Cryptdin (mainly in mice)

Direct membrane disruption via binding to negatively charged microbial membranes, leading to permeabilization and cell death Inhibition of microbial cell wall synthesis Neutralization of pathogenic proteins and toxins Immunomodulation (cytokine release, cell maturation, chemotaxis)