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 beta 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.
Department of Chemistry, Inha University, 253 Younghyong-Dong, Nam-Gu, Inchon-City 402-751, South Korea.
Hyun-Sik
HS
Oh
Seunghee
S
Kim
Hyeongjin
H
Cho
Keun-Hyeung
KH
Lee
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D019476:Insect Proteins / Q000737:chemistry; D008055:Lipids / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D019476:Insect Proteins; D008055:Lipids; C091169:tenecin 1 protein, Tenebrio molitor