Nonactin

About: Nonactin is a research topic. Over the lifetime, 293 publications have been published within this topic receiving 6875 citations.

Freezing and Melting of Lipid Bilayers and the Mode of Action of Nonactin, Valinomycin, and Gramicidin

Abstract: An abrupt loss of effectiveness of the presumed carriers, nonactin and valinomycin, in mediating ion conductance occurred at the same temperature as the membrane fluidity, judged visually, was lost. By contrast, the effects of the presumed channel-former, gramicidin, were the same on solid and liquid membranes. Taken together, these findings imply that freezing the membrane primarily reduces the mobility of these antibiotics with little effect on their solubility.

Effect of phloretin on the permeability of thin lipid membranes.

Abstract: Phloretin dramatically increases cation conductances and decreases anion conductances of membranes treated with ion carriers (nonactin, valinomycin, carbonyl-cyanide-m-chlorophenylhydrazone [CCCP], and Hg(C6F5)2) or lipophilic ions (tetraphenylarsonium [tphAs+] and tetraphenylborate [TPhB-]). For example, on phosphatidylethanolamine membranes, 10(-4) M phloretin increases K+ -nonactin and TPhAs+ conductances and decreases CCCP- and TPhB- conductances 10(3)-fold; on lecithin: cholesterol membranes, it increases K+-nonactin conductance 10(5)-fold and decreases CCCP- conductance 10(3)-fold. Similar effects are obtained with p- and m-nitrophenol at 10(-2) M. These effects are produced by the un-ionized form of phloretin and the nitrophenols. We believe that phloretin, which possesses a large dipole moment, adsorbs and orients at the membrane surface to introduce a dipole potential of opposite polarity to the preexisting positive one, thus increasing the partition coefficient of cations into the membrane interior and decreasing the partition coefficient of anions. (Phloretin may also increase the fluidity of cholesterol-containing membranes; this is manifested by its two- to three-fold increase in nonelectrolyte permeability and its asymmetrical effect on cation and anion conductances in cholesterol-containing membranes.) It is possible that pholoretin's inhibition of chloride, urea, and glucose transport in biological membranes results from the effects of these intense intrafacial dipole fields on the translocator(s) of these molecules.

The effects of the macrotetralide actin antibiotics on the electrical properties of phospholipid bilayer membranes

Abstract: This paper, the last in a series of three, characterizes the electrical properties of phospholipid bilayer membranes exposed to aqueous solutions containing nonactin, monactin, dinactin, and trinactin and Li+, Na+, K+, Rb+, Cs+, and NH4+ ions. Not only are both the membrane resistance at zero current and the membrane potential at zero current found to depend on the aqueous concentrations of antibiotic and ions in the manner expected from the theory of the first paper, but also these measurements are demonstrated to be related to each other in the manner required by this theory for “neutral carriers”. To verify that these antibiotics indeed are free to move as carriers of cations, cholesterol was added to the lipid to increase the “viscosity” of the interior of the membrane. Cholesterol decreased by several orders of magnitude the ability of the macrotetralide antibiotics to lower the membrane resistance; nevertheless, the permeability ratios and conductance ratios remained exactly the same as in cholesterolfree membranes. These findings are expected for the “carrier” mechanism postulated in the first paper and serve to verify it. Lastly, the observed effects of nonactin, monactin, dinactin, and trinactin on bilayers are compared with those predicted in the preceding paper from the salt-extraction equilibrium constants measured there; and a close agreement is found. These results show that the theory of the first paper satisfactorily predicts the effects of the macrotetralide actin antibiotics on the electrical properties of phospholipid bilayer membranes, using only the thermodynamic constants measured in the second paper. It therefore seems reasonable to conclude that these antibiotics produce their characteristic effects on membranes by solubilizing cations therein as mobile positively charged complexes.

Ion binding by synthetic macrocyclic compounds.

Abstract: The existence of synthetic macrocyclic molecules with hydrophilic cavities containing multiple binding atoms and with hydrophobic exteriors gives rise to extraordinary possibilities with respect to the design and synthesis of molecules with specific cation and anion binding properties. The preparation of many new macrocyclic compounds has recently been reported, but few practical applications for them have been suggested. From the information available, it is becoming clear that it should be possible to synthesize macrocycles that will have specified, or selected, ion binding properties. Cavity size can be varied to accommodate only those cations or anions within a specified narrow band of sizes. Numbers and types of coordinating atoms can be chosen to give essentially electrostatic or covalent bonding or a combination of the two in a metalmacrocycle complex. The metal ligand bond appears to be predominantly ionic in the case of the cyclic polyethers but the covalent character increases on substitution of sulfur or nitrogen for oxygen donor atoms. The essential hydrophobic exteriors of the macrocycles can be modified by the addition of side chains and groups to facilitate the solution of anions and cations in organic solvents. The structures of many macrocycles can be made to approximate naturally occurring molecules, that is, cyclic polyethers similar to macrocyclic antibiotics of the valinomycin and nonactin types and cyclic polyamines similar to porphyrins. Macrocycles are also useful as model compounds for the study of metal interactions with biological systems. The synthetic macrocycles thus represent an intriguing new area of coordination chemistry, the systematic study of which should lead to many interesting and useful chemical applications in the field of metal complexation in solution.