Antimicrobial Peptide (AMP): Definition

Detailed Explanation

Antimicrobial peptides (AMPs) are evolutionarily ancient weapons found in virtually every multicellular organism, from insects and plants to fish, amphibians, and humans. Most AMPs are short (12–50 amino acids), positively charged (net charge +2 to +9 from arginine and lysine residues), and amphipathic — one face is hydrophobic and the other hydrophilic when folded into an alpha helix. This combination of positive charge and amphipathicity allows them to selectively target negatively charged bacterial membranes while sparing the neutral cholesterol-rich membranes of host cells.

AMPs kill primarily through membrane disruption via several proposed mechanisms: the barrel-stave model (peptides insert perpendicular to the membrane to form transmembrane pores), the toroidal pore model (peptides and lipid headgroups together form a pore lined by both peptide and lipid), and the carpet model (peptides accumulate on the membrane surface until a critical concentration causes detergent-like dissolution). Some AMPs also have intracellular targets — inhibiting DNA, RNA, or protein synthesis after entering the cell.

Humans produce several AMP families. Cathelicidins (LL-37 is the sole human member) are stored in neutrophil granules and produced by epithelial cells. α-Defensins (HNP-1 to HNP-4, HD-5, HD-6) protect neutrophils and the intestinal lining. β-Defensins (hBD-1 to hBD-4) defend skin, airways, and the urogenital tract. Because AMPs use physical membrane disruption rather than targeting specific metabolic enzymes, bacteria develop resistance far more slowly than to conventional antibiotics, making AMPs promising candidates for next-generation anti-infective drugs. The Antimicrobial Peptide Database (APD) catalogs over 3,000 natural AMPs.

Key Facts

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