Rational design of anti-microbial peptides with enhanced activity and low cytotoxicity based on the structure of the arginine/histidine-rich peptide, chensinin-1.
OBJECTIVE
To understand the structure-activity relationship of chensinin-1, a anti-microbial peptide (AMP) with an unusual structure, and to develop novel AMPs as therapeutic agents.


RESULTS
A series of chensinin-1 analogues were designed and synthesized by one to three replacement of glycines with leucines at the hydrophilic face of chensinin-1 or rearrangement of some of the residues in its sequence. Circular dichroism spectroscopy showed that the analogues adopted α-helical-type conformations in 50% trifluoroethanol/water but adopted β-strand-type conformations in 30 mmol l(-1) sodium dodecyl sulphate. The anti-microbial activities of the peptides against Gram-positive bacteria increased 5- to 30-fold, and these increases paralleled the increases in the peptides' hydrophobicities. Their haemolytic activities also increased. Amphipathicities had little influence on the bactericidal activity of chensinin-1. All peptides caused leakage of calcein entrapped in negatively charged liposomes although with different efficiencies. The peptides did not induce leakage of calcein from uncharged liposomes.


CONCLUSIONS
Peptide adopted an aperiodic structure can improve the anti-microbial potency by increasing peptide hydrophobicity. Its target is bacteria plasma membrane.


CONCLUSIONS
Chensinin-1 can act as a new lead molecule for the study of AMPs with atypical structures.
Faculty of Life Science, Liaoning Normal University, Dalian, China. djshang@lnnu.edu.cn
D
D
Shang
Y
Y
Sun
C
C
Wang
L
L
Ma
J
J
Li
X
X
Wang
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001120:Arginine / Q000737:chemistry; D002462:Cell Membrane / Q000187:drug effects; D002942:Circular Dichroism; D015195:Drug Design; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006461:Hemolysis; D006639:Histidine / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D008081:Liposomes; D010455:Peptides; D006639:Histidine; D001120:Arginine