Lipopeptide
A peptide covalently linked to a fatty acid. Daptomycin is an approved lipopeptide antibiotic whose lipid chain enables bacterial membrane disruption. The lipidation concept extends to drug design — semaglutide and liraglutide use fatty acid chains for albumin binding and half-life extension.
Technical Context
Lipopeptide structural biology: the peptide component provides receptor/target specificity while the lipid component facilitates membrane interaction. Daptomycin's mechanism: in the presence of calcium ions, daptomycin oligomerises and inserts its lipid tail into the bacterial cytoplasmic membrane, forming pores that depolarise the membrane and disrupt ion gradients — causing rapid cell death without lysis (this may reduce endotoxin release compared to lytic antibiotics). The lipidation strategy in drug design: fatty acid chain length affects pharmacokinetics — C-16 palmitic acid (liraglutide, half-life ~13h) vs C-18 fatty diacid (semaglutide, half-life ~165h). Longer fatty acids generally provide stronger albumin binding but may reduce aqueous solubility. The position and chemistry of fatty acid attachment (direct vs via linker) also affect receptor binding and albumin interaction.