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Review
. 1999 Jun;43(6):1317-23.
doi: 10.1128/AAC.43.6.1317.

Peptide antibiotics

R E Hancock  1 , D S Chapple
Affiliations
Review

Peptide antibiotics

R E Hancock et al. Antimicrob Agents Chemother. 1999 Jun.
No abstract available

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Figures

FIG. 1
FIG. 1
Molecular model of a defensin, human neutrophil peptide (HNP-1), based on the two-dimensional nuclear magnetic resonance-derived structure. The ribbon structures are β-strands connected by tubes of β-turn and random structures and stabilized by three intrachain disulfide bridges. The side chains of the positively charged lysine residues are shown as extended Y-shaped structures.
FIG. 2
FIG. 2
Proposed mechanism of interaction of cationic antimicrobial peptides with the cell envelope of gram-negative bacteria. Passage across the outer membrane is proposed to occur by self-promoted uptake. According to this hypothesis, unfolded cationic peptides are proposed to associate with the negatively charged surface of the outer membrane and either neutralize the charge over a patch of the outer membrane, creating cracks through which the peptide can cross the outer membrane (A), or actually bind to the divalent cation binding sites on LPS and disrupt the membrane (B). Once the peptide has transited the outer membrane, it will bind to the negatively charged surface of the cytoplasmic membrane, created by the headgroups of phosphatidylglycerol and cardiolipin, and the amphipathic peptide will insert into the membrane interface (the region where the phospholipid headgroups meet the fatty acyl chains of the phospholipid membrane) (C). It is not known at which point in this process the peptide actually folds into its amphipathic structure (i.e., during transit across the outer membrane or during insertion into the cytoplasmic membrane). Many peptide molecules will insert into the membrane interface and are proposed to then either aggregate into a micelle-like complex which spans the membrane (D) or flip-flop across the membrane under the influence of the large transmembrane electrical potential gradient (approximately −140 mV) (E). The micelle-like aggregates (D) are proposed to have water associated with them, and this provides channels for the movement of ions across the membrane and possibly leakage of larger water-soluble molecules. These aggregates would be variable in size and lifetime and will dissociate into monomers that may be disposed at either side of the membrane. The net effect of D and E is that some monomers will be translocated into the cytoplasm and can dissociate from the membrane and bind to cellular polyanions such as DNA and RNA (F).
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