Photogating of ionic currents across a lipid bilayer.

Self Cite

652

492

The D enantiomers of three naturally occurring antibiotics-cecropin A, magainin 2 amide, and melittin-were synthesized. In addition, the D enantiomers of two synthetic chimeric cecropin-melittin hybrid peptides were prepared. Each D isomer was shown by circular dichroism to be a mirror image of the corresponding L isomer in several solvent mixtures. In 20% hexafluoro-2-propanol the peptides contained 43-75% a-helix. The all-D peptides were resistant to enzymatic degradation. The peptides produced single-channel conductances in planar lipid bilayers, and the D and L enantiomers caused equivalent amounts of electrical conductivity. All of the peptides were potent antibacterial agents against representative Gram-negative and Gram-positive species. The D and L enantiomers of each peptide pair were equally active, within experimental error. Sheep erythrocytes were lysed by both D-and L-melittin but not by either isomer of cecropin A, magainin 2 amide, or the hybrids cecropin A-(1-13)-melittin-(1-13)-NH2 or cecropin A-(1-8)-melittin-(1-18)-NH2. The infectivity of the bloodstream form of the malaria parasite Plasmodium falciparum was also inhibited by the D and L hybrids. It is suggested that the mode of action of these peptides on the membranes of bacteria, erythrocytes, plasmodia, and artificial lipid bilayers may be similar and involves the formation of ion-channel pores spanning the membranes, but without specific interaction with chiral receptors or enzymes.The cecropins (1, 2) and several other antibiotic peptides of the animal kingdom, including defensins (3), magainins (4), and the bee venom toxin melittin (5), are thought to function through the formation of ion channels in lipid membranes. This idea has been based on recent studies of electrical conductivity in artificial lipid bilayers (3,(6)(7)(8), where activity is a function of the structure of the peptide and the composition of the membrane lipids. The bilayer lipids and cell membranes are chiral and contain many asymmetric centers. It has been generally assumed that the chirality of the membrane would require a specific chirality ofthe peptide for it to be active, in much the same way that peptide hormones are required to fit with the conformation of their natural receptors or for a substrate and enzyme to form a tight stereospecific complex. However, we have suggested that these peptide antibiotics can exert their effect without requiring a specific target receptor on the cell membrane (7, 9).The purpose of the present study was to test this assumption by the synthesis of the all-D enantiomers of several natural, all-L peptide antibiotics and some of their active analogs. These D stereoisomers would be expected to assume equivalent, but mirror image, conformations when placed in the same environment as the all-L peptides. If a close molecular contact with the chiral components of the cell membrane is required, the D enantiomers would be expected to be inactive. However, if the interaction of the peptide with the membrane is only between achiral...

Section: Methodsmentioning

confidence: 99%

“…Electrical Conductivity Measurements. The equipment and procedures were similar to those described previously (7,16 To whom reprint requests should be addressed. …”

mentioning

confidence: 99%

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

Wade

Boman

Wåhlin

et al. 1990

Self Cite

652

492

“…Inspired by biological systems, the introduction of specific interactions is a route toward using the facile and energetically favorable production capabilities to self-assemble materials (8). Exploitation of nonspecific intermolecular interactions has resulted also in the formation of molecular electronic devices (9)(10)(11). We have used self-assembly to form a square planar array of nine porphyrins mediated by coordination of exocyclic pyridyl groups on three different porphyrins to 12 trans-palladium dichlorides (12,13).…”

mentioning

confidence: 99%

Designing supramolecular porphyrin arrays that self-organize into nanoscale optical and magnetic materials

Drain

Batteas

Flynn

et al. 2002

132

Tessellation of nine free-base porphyrins into a 3 ؋ 3 array is accomplished by the self-assembly of 21 molecular entities of four different kinds, one central, four corner, and four side porphyrins with 12 trans Pd(II) complexes, by specifically designed and targeted intermolecular interactions. Strikingly, the self-assembly of 30 components into a metalloporphyrin nonamer results from the addition of nine equivalents of a first-row transition metal to the above milieu. In this case each porphyrin in the nonameric array coordinates the same metal such as Mn(II), Ni(II), Co(II), or Zn(II). This feat is accomplished by taking advantage of the highly selective porphyrin complexation kinetics and thermodynamics for different metals. In a second, hierarchical self-assembly process, nonspecific intermolecular interactions can be exploited to form nanoscaled three-dimensional aggregates of the supramolecular porphyrin arrays. In solution, the size of the nanoscaled aggregate can be directed by fine-tuning the properties of the component macrocycles, by choice of metalloporphyrin, and the kinetics of the secondary self-assembly process. As precursors to device formation, nanoscale structures of the porphyrin arrays and aggregates of controlled size may be deposited on surfaces. Atomic force microscopy and scanning tunneling microscopy of these materials show that the choice of surface (gold, mica, glass, etc.) may be used to modulate the aggregate size and thus its photophysical properties. Once on the surface the materials are extremely robust.

“…This self-organizing device used the interfacial photo-induced -fold more lipophilic ions across the BLM than formed by the photochemical event. A Grotthus-type mechanism was proposed to be the basis of conduction across the bilayer, wherein the initial charge transfer led to the spontaneous formation of an ion chain of alternating lipophilic porphyrin cations and lipophilic anions that spans the bilayer (11,12). Later devices (13,14) used other charge carriers such as C 60 and protonophores, which led to a device that pumped protons across the membrane (15,16).…”

Section: Design Features and Principlesmentioning

confidence: 99%

“…The incorporation of porphyrins into bilayer lipid membranes (BLM) to study interfacial electron transfer reactions to aqueous quinones eventually led to the formation of a molecular electronic device that functioned as a photogated transistor (10)(11)(12). This self-organizing device used the interfacial photo-induced -fold more lipophilic ions across the BLM than formed by the photochemical event.…”

Section: Design Features and Principlesmentioning

confidence: 99%

Self-organization of self-assembled photonic materials into functional devices: Photo-switched conductors

Drain

2002

Linear porphyrin arrays self-assembled by either hydrogen bonding or metal ion coordination self-organize into lipid bilayer membranes. The length of the transmembrane assemblies is determined both by the thermodynamics of the intermolecular interactions in the supermolecule and by the dimension and physical chemical properties of the bilayer. Thus, the size of the porphyrin assembly can self-adjust to the thickness of the bilayer. An aqueous electron acceptor is placed on one side of the membrane and an electron donor is placed on the opposite side. When illuminated with white light, substantial photocurrents are observed. Only the assembled structures give rise to the photocurrent, as no current is observed from any of the component molecules. The fabrication of this photogated molecular electronic conductor from simple molecular components exploits several levels of self-assembly and selforganization.