scholarly journals The Ion Permeability Induced in Thin Lipid Membranes by the Polyene Antibiotics Nystatin and Amphotericin B

1970 ◽  
Vol 56 (1) ◽  
pp. 100-124 ◽  
Author(s):  
Albert Cass ◽  
Alan Finkelstein ◽  
Vivian Krespi
Keyword(s):  
Amphotericin B ◽  
Lipid Membranes ◽  
Ion Selectivity ◽  
Membrane Conductance ◽  
Temperature Sensitive ◽  
Hydroxyl Groups ◽  
Large Power ◽  
Polyene Antibiotics ◽  
Cation Selectivity ◽  
Anion Selectivity

Characteristics of nystatin and amphotericin B action on thin (<100 A) lipid membranes are: (a) micromolar amounts increase membrane conductance from 10-8 to over 10-2 Ω-1 cm-2; (b) such membranes are (non-ideally) anion selective and discriminate among anions on the basis of size; (c) membrane sterol is required for action; (d) antibiotic presence on both sides of membrane strongly favors action; (e) conductance is proportional to a large power of antibiotic concentration; (f) conductance decreases ∼104 times for a 10°C temperature rise; (g) kinetics of antibiotic action are also very temperature sensitive; (h) ion selectivity is pH independent between 3 and 10, but (i) activity is reversibly lost at high pH; (j) methyl ester derivatives are fully active; N-acetyl and N-succinyl derivatives are inactive; (k) current-voltage characteristic is nonlinear when membrane separates nonidentical salt solutions. These characteristics are contrasted with those of valinomycin. Observations (a)–(g) suggest that aggregates of polyene and sterol from opposite sides of the membrane interact to create aqueous pores; these pores are not static, but break up (melt) and reform continuously. Mechanism of anion selectivity is obscure. Observations (h)–(j) suggest—NH3+ is important for activity; it is probably not responsible for selectivity, particularly since four polyene antibiotics, each containing two—NH3+ groups, induce ideal cation selectivity. Possibly the many hydroxyl groups in nystatin and amphotericin B are responsible for anion selectivity. The effects of polyene antibiotics on thin lipid membranes are consistent with their action on biological membranes.

scholarly journals Tuning the ion selectivity of glutamate transporter–associated uncoupled conductances

2016 ◽  
Vol 148 (1) ◽  
pp. 13-24 ◽  
Author(s):  
Rosemary J. Cater ◽  
Robert J. Vandenberg ◽  
Renae M. Ryan
Keyword(s):  
Excitatory Amino Acid ◽  
Ion Selectivity ◽  
Glutamate Transporter ◽  
Amino Acid Transporters ◽  
Primary Role ◽  
Cation Selectivity ◽  
Anion Selectivity ◽  
Transport Domain ◽  
Cl Conductance

The concentration of glutamate within a glutamatergic synapse is tightly regulated by excitatory amino acid transporters (EAATs). In addition to their primary role in clearing extracellular glutamate, the EAATs also possess a thermodynamically uncoupled Cl− conductance. This conductance is activated by the binding of substrate and Na+, but the direction of Cl− flux is independent of the rate or direction of substrate transport; thus, the two processes are thermodynamically uncoupled. A recent molecular dynamics study of the archaeal EAAT homologue GltPh (an aspartate transporter from Pyrococcus horikoshii) identified an aqueous pore at the interface of the transport and trimerization domains, through which anions could permeate, and it was suggested that an arginine residue at the most restricted part of this pathway might play a role in determining anion selectivity. In this study, we mutate this arginine to a histidine in the human glutamate transporter EAAT1 and investigate the role of the protonation state of this residue on anion selectivity and transporter function. Our results demonstrate that a positive charge at this position is crucial for determining anion versus cation selectivity of the uncoupled conductance of EAAT1. In addition, because the nature of this residue influences the turnover rate of EAAT1, we reveal an intrinsic link between the elevator movement of the transport domain and the Cl− channel.

scholarly journals Structure-Antifungal Activity Relationships of Polyene Antibiotics of the Amphotericin B Group

2013 ◽  
Vol 57 (8) ◽  
pp. 3815-3822 ◽  
Author(s):  
Anna N. Tevyashova ◽  
Evgenia N. Olsufyeva ◽  
Svetlana E. Solovieva ◽  
Svetlana S. Printsevskaya ◽  
Marina I. Reznikova ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Cooh Group ◽  
Hydroxyl Groups ◽  
Activity Data ◽  
Oh Groups ◽  
Polyene Antibiotics ◽  
High Antifungal Activity

ABSTRACTA comprehensive comparative analysis of the structure-antifungal activity relationships for the series of biosynthetically engineered nystatin analogues and their novel semisynthetic derivatives, as well as amphotericin B (AMB) and its semisynthetic derivatives, was performed. The data obtained revealed the significant influence of the structure of the C-7 to C-10 polyol region on the antifungal activity of these polyene antibiotics. Comparison of positions of hydroxyl groups in the antibiotics andin vitroantifungal activity data showed that the most active are the compounds in which hydroxyl groups are in positions C-8 and C-9 or positions C-7 and C-10. Antibiotics with OH groups at both C-7 and C-9 had the lowest activity. The replacement of the C-16 carboxyl with methyl group did not significantly affect thein vitroantifungal activity of antibiotics without modifications at the amino group of mycosamine. In contrast, the activity of the N-modified derivatives was modulated both by the presence of CH3or COOH group in the position C-16 and by the structure of the modifying substituent. The most active compounds were testedin vivoto determine the maximum tolerated doses and antifungal activity on the model of candidosis sepsis in leukopenic mice (cyclophosphamide-induced). Study of our library of semisynthetic polyene antibiotics led to the discovery of compounds, namely,N-(l-lysyl)-BSG005 (compound 3n) and, especially,l-glutamate of 2-(N,N-dimethylamino)ethyl amide of S44HP (compound 2j), with high antifungal activity that were comparable inin vitroandin vivotests to AMB and that have better toxicological properties.

scholarly journals The Interaction of Polyene Antibiotics with Thin Lipid Membranes

1968 ◽  
Vol 52 (2) ◽  
pp. 300-325 ◽  
Author(s):  
Thomas E. Andreoli ◽  
Marcia Monahan
Keyword(s):  
Amphotericin B ◽  
Lipid Membranes ◽  
Sheep Erythrocyte ◽  
Cholesterol Content ◽  
Transference Numbers ◽  
Ionic Selectivity ◽  
Antibiotic Concentration ◽  
Polyene Antibiotics ◽  
Cyclic Polyene ◽  
Membrane Bound

Optically black, thin lipid membranes prepared from sheep erythrocyte lipids have a high dc resistance (Rm ≅ 108 ohm-cm2) when the bathing solutions contain NaCl or KCl. The ionic transference numbers (Ti) indicate that these membranes are cation-selective (TNa ≅ 0.85; TCl ≅ 0.15). These electrical properties are independent of the cholesterol content of the lipid solutions from which the membranes are formed. Nystatin, and probably amphotericin B, are cyclic polyene antibiotics containing ≈36 ring atoms and a free amino and carboxyl group. When the lipid solutions used to form membranes contained equimolar amounts of cholesterol and phospholipid, these antibiotics reduced Rm to ≈102 ohm-cm2; concomitantly, TCl became ≅0.92. The slope of the line relating log Rm and log antibiotic concentration was ≅4.5. Neither nystatin (2 x 10-5 M) nor amphotericin B (2 x 10-7 M) had any effect on membrane stability. The antibiotics had no effect on Rm or membrane permselectivity when the lipids used to form membranes were cholesterol-depleted. Filipin (10-5 M), an uncharged polyene with 28 ring atoms, produced striking membrane instability, but did not affect Rm or membrane ionic selectivity. These data suggest that amphotericin B or nystatin may interact with membrane-bound sterols to produce multimolecular complexes which greatly enhance the permeability of such membranes for anions (Cl-, acetate), and, to a lesser degree, cations (Na+, K+, Li+).

scholarly journals The Water and Nonelectrolyte Permeability Induced in Thin Lipid Membranes by the Polyene Antibiotics Nystatin and Amphotericin B

1970 ◽  
Vol 56 (1) ◽  
pp. 125-145 ◽  
Author(s):  
Ronald Holz ◽  
Alan Finkelstein
Keyword(s):  
Amphotericin B ◽  
Lipid Membranes ◽  
Permeability Coefficient ◽  
Membrane Conductance ◽  
Red Cell Membrane ◽  
Water Permeability Coefficient ◽  
Permeability Increase ◽  
Hydrophilic Solutes ◽  
Human Red Cell Membrane ◽  
Nonelectrolyte Permeability

Nystatin and amphotericin B increase the permeability of thin (<100 A) lipid membranes to ions, water, and nonelectrolytes. Water and nonelectrolyte permeability increase linearly with membrane conductance (i.e., ion permeability). In the unmodified membrane, the osmotic permeability coefficient, Pf, is equal to the tagged water permeability coefficient, (Pd)w; in the nystatin- or amphotericin B-treated membrane, Pf/(Pd)w ≈ 3. The unmodified membrane is virtually impermeable to small hydrophilic solutes, such as urea, ethylene glycol, and glycerol; the nystatin- or amphotericin B-treated membrane displays a graded permeability to these solutes on the basis of size. This graded permeability is manifest both in the tracer permeabilities, Pd, and in the reflection coefficients, σ (Table I). The "cutoff" in permeability occurs with molecules about the size of glucose (Stokes-Einstein radius ≊ 4 A). We conclude that nystatin and amphotericin B create aqueous pores in thin lipid membranes; the effective radius of these pores is approximately 4 A. There is a marked similarity between the permeability of a nystatin- or amphotericin B-treated membrane to water and small hydrophilic solutes and the permeability of the human red cell membrane to these same molecules.

An effect of antibiotic amphotericin B on ion transport across model lipid membranes and tonoplast membranes

2005 ◽  
Vol 70 (5) ◽  
pp. 668-675 ◽  
Author(s):  
Monika Hereć ◽  
Halina Dziubińska ◽  
Kazimierz Trębacz ◽  
Jacek W. Morzycki ◽  
Wiesław I. Gruszecki
Keyword(s):  
Ion Transport ◽  
Amphotericin B ◽  
Lipid Membranes ◽  
Model Lipid Membranes

scholarly journals Layered double hydroxide membrane with high hydroxide conductivity and ion selectivity for energy storage device

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Hu ◽  
Xiaomin Tang ◽  
Qing Dai ◽  
Zhiqiang Liu ◽  
Huamin Zhang ◽  
...  
Keyword(s):  
Energy Storage ◽  
High Performance ◽  
Ion Selectivity ◽  
Storage Device ◽  
Hydroxyl Groups ◽  
Flow Battery ◽  
Energy Storage Devices ◽  
Storage Devices ◽  
Ions Transport ◽  
Double Hydroxides

AbstractMembranes with fast and selective ions transport are highly demanded for energy storage devices. Layered double hydroxides (LDHs), bearing uniform interlayer galleries and abundant hydroxyl groups covalently bonded within two-dimensional (2D) host layers, make them superb candidates for high-performance membranes. However, related research on LDHs for ions separation is quite rare, especially the deep-going study on ions transport behavior in LDHs. Here, we report a LDHs-based composite membrane with fast and selective ions transport for flow battery application. The hydroxide ions transport through LDHs via vehicular (standard diffusion) & Grotthuss (proton hopping) mechanisms is uncovered. The LDHs-based membrane enables an alkaline zinc-based flow battery to operate at 200 mA cm−2, along with an energy efficiency of 82.36% for 400 cycles. This study offers an in-depth understanding of ions transport in LDHs and further inspires their applications in other energy-related devices.

scholarly journals Structure and Antimicrobial Properties of Monensin A and Its Derivatives: Summary of the Achievements

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Daniel Łowicki ◽  
Adam Huczyński
Keyword(s):  
Antimicrobial Activity ◽  
Lipid Membranes ◽  
Antimicrobial Properties ◽  
Biological Properties ◽  
Sodium Cation ◽  
Hydroxyl Groups ◽  
Carboxyl Group ◽  
Growth Promoter ◽  
Monensin A

In this paper structural and microbiological studies on the ionophorous antibiotic monensin A and its derivatives have been collected. Monensin A is an ionophore which selectively complexes and transports sodium cation across lipid membranes, and therefore it shows a variety of biological properties. This antibiotic is commonly used as coccidiostat and nonhormonal growth promoter. The paper focuses on both the latest and earlier achievements concerning monensin A antimicrobial activity. The activities of monensin derivatives, including modifications of hydroxyl groups and carboxyl group, are also presented.

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