Role of amino acid residues within the disulfide loop of thanatin, a potent antibiotic peptide.
Thanatin, a 21-residue peptide, is an inducible insect peptide with a broad range of activity against bacteria and fungi. It has a C-terminal disulfide loop, like the frog skin secretion antimicrobial peptides of the brevinin family. In this study, we tried to find the effect of a number of amino acids between the disulfide bond. Thanatin showed stronger antibacterial activity to Gram negative bacteria than other mutants, except Th1; whereas, the mutant peptides with deletion had higher activity to Gram positive bacteria than thanatin. An increase in the number of amino acid(s) using the alanine residue decreased the antibacterial activity in all of the bacteria. Th1 with deletion of threonine at position 15 (Thr(1)(2)) showed similar antibacterial activity against Gram-negative bacteria, but had higher activity against the Gram positive bacteria. In order to study the structure-function relationship, we measured liposome disruption by the peptides and CD spectra of the peptides. Th1 also showed the highest liposome leaking activity and alpha-helical propensity in the sodium dodecyl sulfate solution, compared with other peptides. Liposome disruption activity was closely correlated with the anti-Gram positive bacterial activity. All of the peptides showed no hemolytic activity. Th1 was considered to be useful as an antimicrobial peptide with broad spectrum without toxicity
Lee
Myung Kyu
MK
Proteome Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yusong, P.O. Box 115, Taejon 305-600, Korea. mklee@mail.kribb.re.kr
Cha
Lina
L
Lee
Si Hyung
SH
Hahm
Kyung-Soo
KS
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002942:Circular Dichroism; D004220:Disulfides / Q000737:chemistry*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004220:Disulfides; D008081:Liposomes; D010456:Peptides, Cyclic; C098076:thanatin