From "carpet" mechanism to de-novo designed diastereomeric cell-selective antimicrobial peptides.
Living organisms of all types produce a large repertoire of gene-encoded, net positively charged, antimicrobial peptides as part of their innate immunity to microbial invasion. Despite significant variations in composition, length and secondary structure most antimicrobial peptides are active in micromolar concentrations, suggesting a common general mechanism for their mode of action. Many antimicrobial peptides bind bacterial phospholipid membranes up to a threshold concentration, followed by membrane permeation/disintegration (the "carpet" mechanism). Recent data suggest that the details of the permeation pathways may vary for different peptides and are assigned to different modes of action. Accumulating data reveal that the molecular basis for cell selectivity is the ability of peptides to specifically bind the negatively charged bacterial membrane, as well as their oligomeric state in solution and in the membrane. Based on the "carpet" mechanism and the role of the peptide oligomeric state, a novel group of diastereomeric (containing D- and L-amino acids) antimicrobial peptides were developed. These peptides may serve as promising templates for the future designs of antimicrobial peptides.
Shai
Y
Y
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100 Israel. Yechiel.Shai@weizmann.ac.il
Oren
Z
Z
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology; D002477:Cells / Q000378:metabolism*; D003500:Cyclization; D015195:Drug Design; D006868:Hydrolysis; D007473:Ion Channels / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides; D012680:Sensitivity and Specificity; D012996:Solutions / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D007473:Ion Channels; D010455:Peptides; D012996:Solutions