All-D amino acid-containing channel-forming antibiotic peptides.

摘要: The D enantiomers of three naturally occurring antibiotics--cecropin A, magainin 2 amide, and melittin--were synthesized. In addition, the two synthetic chimeric cecropin-melittin hybrid peptides were prepared. Each isomer was shown by circular dichroism to be a mirror image corresponding L in several solvent mixtures. 20% hexafluoro-2-propanol contained 43-75% alpha-helix. all-D resistant enzymatic degradation. produced single-channel conductances planar lipid bilayers, caused equivalent amounts electrical conductivity. All potent antibacterial agents against representative Gram-negative Gram-positive species. each peptide pair equally active, within experimental error. Sheep erythrocytes lysed both D- L-melittin but not either cecropin or hybrids A-(1-13)-melittin-(1-13)-NH2 A-(1-8)-melittin-(1-18)-NH2. infectivity bloodstream form malaria parasite Plasmodium falciparum also inhibited hybrids. It is suggested that mode action these on membranes bacteria, erythrocytes, plasmodia, artificial bilayers may similar involves formation ion-channel pores spanning membranes, without specific interaction with chiral receptors enzymes.