Development of novel lipid–peptide hybrid compounds with antibacterial activity from natural cationic antibacterial peptides

Seven depsipeptides were synthesized by appending seven amino acids (Lys, Leu, Val, Phe, Ser, Gln, and Pro) at the N-terminus of the active fragment [TE-(33-43)], respectively corresponding to the C-terminal β sheet domain of tenecin 1, an antibacterial protein and their activities were measured against Staphylococcus aureus. Considering the relationship between the activity and the characteristic of amino acid at the N-terminal of the peptide, novel derivatives were designed and synthesized from TE-(33-43) by introduction of fatty acids at the N-terminal. In this process, we synthesized novel lipid–peptide hybrid compounds with a potent antibacterial activity and more improved bioavailabilities. We characterized the important structural parameters of the lipid–peptide hybrid compounds for the antibacterial activities.