The cecropins: An example of the use of peptide synthesis to study a biochemical problem

The antibiotic activity of cationic linear amphipathic peptides: lessons from the action of leucine/lysine copolymers on bacteria of the class Mollicutes

“…The activity varied with peptide length, the optimum occurring for the 15-residue ideally amphipathic a-helical structure [LK15(3.6)] the activity of which was similar to that of melittin, a bee venom peptide known as one of the most efficient natural peptides in killing bacteria [8,[39][40][41].…”

“…This concept, which has been useful in the field of peptidic cytotoxins to develop new analogues, and to better understand their mode of action [5][6][7], is still the basis for the rational design of new antimicrobial compounds, i.e. analogues or chimeras of natural products [8], or radically new molecules [9,10].The need to understand their mode of action and improve their efficacy and/or selectivity towards microorganisms led to the synthesis of new active peptides, made possible largely by the progress in solid state synthesis. As a result, a large wealth of information was obtained on many natural peptides endowed with cytotoxic (including antimicrobial) activity.…”

Permeabilization of the Mitochondrial Inner Membrane by Short Cecropin‐A–Melittin Hybrid Peptides

“…However, their mode of action differs from that of CA(1-8)M(1-18)-NH,, since they require a much higher concentration and the presence of heparin. While long peptides are able to form ahelical structures which would span the membrane and hence could form channels, the action of short peptides would require either the stacking of monomers (Merrifield et al, 1991), adoption of extended (3,0) helices (Andreu et al, 1992), or simply the disintegration of the membrane due to a detergent-like action. In the mitochondrial model used in this work, the lack of specificity of the channels formed (swelling is observed both in salts and sucrose) would, in our view, favor this latter possibility.…”

“…The elimination of the C-terminal end from the melittin molecule greatly diminishes its hemolytic activity. Some of the active peptides of these series have a sequence shorter than that required to span the thickness of the bilayer; thus, their mode of action must differ from that of the parental peptides (Merrifield et al, 1991 ;Andreu et a]., 1992).…”

D-Cecropin B: proteolytic resistance, lethality for pathogenic fungi and binding properties

“…The microbicidal properties of these peptides are believed to be mediated by pore formation in cell membranes or the disintegration of the cell membrane by disruption of lipid bilayer packing [22 -24]. Microbial lysis appears to depend on the hydrophobic environment of the membrane and the conformation that the peptide chain and its aggregates can assume in order to promote ion permeability and cell death [26]. However, Wade et al [25] demonstrated that D-enantiomers of cecropin A, maganin-2-amide and melitin would interact with planar lipid bilayers and retain their antibacterial properties.…”