scholarly journals Boosting Anion Transport Activity of Diamidocarbazoles by Electron Withdrawing Substituents

2021 ◽  
Vol 9 ◽  
Author(s):  
Krystyna Maslowska-Jarzyna ◽  
Maria L. Korczak ◽  
Michał J. Chmielewski
Keyword(s):  
Lipid Bilayers ◽  
Chloride Transport ◽  
Mechanistic Studies ◽  
Transport Activity ◽  
Present Contribution ◽  
Highly Active ◽  
Large Unilamellar Vesicles ◽  
Carrier Mechanism ◽  
Anion Transport Activity ◽  
Electron Withdrawing Substituents

Artificial chloride transporters have been intensely investigated in view of their potential medicinal applications. Recently, we have established 1,8-diamidocarbazoles as a versatile platform for the development of active chloride carriers. In the present contribution, we investigate the influence of various electron-withdrawing substituents in positions 3 and 6 of the carbazole core on the chloride transport activity of these anionophores. Using lucigenin assay and large unilamellar vesicles as models, the 3,6-dicyano- and 3,6-dinitro- substituted receptors were found to be highly active and perfectly deliverable chloride transporters, with EC50,270s value as low as 22 nM for the Cl−/NO3− exchange. Mechanistic studies revealed that diamidocarbazoles form 1:1 complexes with chloride in lipid bilayers and facilitate chloride/nitrate exchange by carrier mechanism. Furthermore, owing to its increased acidity, the 3,6-dinitro- substituted receptor acts as a pH-switchable transporter, with physiologically relevant apparent pKa of 6.4.

scholarly journals Transmembrane Fluoride Transport by a Cyclic Azapeptide With Two β-Turns

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhixing Zhao ◽  
Miaomiao Zhang ◽  
Bailing Tang ◽  
Peimin Weng ◽  
Yueyang Zhang ◽  
...  
Keyword(s):  
Chloride Transport ◽  
Anion Transport ◽  
Bacterial Survival ◽  
Transport Activity ◽  
Selective Electrode ◽  
Design And Synthesis ◽  
Anion Transporters ◽  
Host Compound ◽  
Anion Transport Activity ◽  
Fluoride Ion Selective Electrode

Diverse classes of anion transporters have been developed, most of which focus on the transmembrane chloride transport due to its significance in living systems. Fluoride transport has, to some extent, been overlooked despite the importance of fluoride channels in bacterial survival. Here, we report the design and synthesis of a cyclic azapeptide (a peptide-based N-amidothiourea, 1), as a transporter for fluoride transportation through a confined cavity that encapsulates fluoride, together with acyclic control compounds, the analogs 2 and 3. Cyclic receptor 1 exhibits more stable β-turn structures than the control compounds 2 and 3 and affords a confined cavity containing multiple inner –NH protons that serve as hydrogen bond donors to bind anions. It is noteworthy that the cyclic receptor 1 shows the capacity to selectively transport fluoride across a lipid bilayer on the basis of the osmotic and fluoride ion-selective electrode (ISE) assays, during which an electrogenic anion transport mechanism is found operative, whereas no transmembrane transport activity was found with 2 and 3, despite the fact that 2 and 3 are also able to bind fluoride via the thiourea moieties. These results demonstrate that the encapsulation of an anionic guest within a cyclic host compound is key to enhancing the anion transport activity and selectivity.

scholarly journals Fluorinated synthetic anion carriers: experimental and computational insights into transmembrane chloride transport

2019 ◽  
Vol 10 (7) ◽  
pp. 1976-1985 ◽  
Author(s):  
Michael J. Spooner ◽  
Hongyu Li ◽  
Igor Marques ◽  
Pedro M. R. Costa ◽  
Xin Wu ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Cell Membranes ◽  
Chloride Transport ◽  
Anion Transporters ◽  
Highly Active ◽  
Active Anion

A series of fluorinated tripodal tris-thioureas function as highly active anion transporters across lipid bilayers and cell membranes.

scholarly journals How Insertion of a Single Tryptophan in the N-Terminus of a Cecropin A-Melittin Hybrid Peptide Changes Its Antimicrobial and Biophysical Profile

Membranes ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 48
Author(s):  
Ana Rita Ferreira ◽  
Cátia Teixeira ◽  
Carla F. Sousa ◽  
Lucinda J. Bessa ◽  
Paula Gomes ◽  
...  
Keyword(s):  
Electrostatic Interactions ◽  
Bacterial Infections ◽  
Electron System ◽  
Bacterial Membranes ◽  
Highly Active ◽  
Large Unilamellar Vesicles ◽  
Biophysical Profile ◽  
N Terminus ◽  
Lysine Residues ◽  
Preferential Location

In the era of antibiotic resistance, there is an urgent need for efficient antibiotic therapies to fight bacterial infections. Cationic antimicrobial peptides (CAMP) are promising lead compounds given their membrane-targeted mechanism of action, and high affinity towards the anionic composition of bacterial membranes. We present a new CAMP, W-BP100, derived from the highly active BP100, holding an additional tryptophan at the N-terminus. W-BP100 showed a broader antibacterial activity, demonstrating a potent activity against Gram-positive strains. Revealing a high partition constant towards anionic over zwitterionic large unilamellar vesicles and inducing membrane saturation at a high peptide/lipid ratio, W-BP100 has a preferential location for hydrophobic environments. Contrary to BP100, almost no aggregation of anionic vesicles is observed around saturation conditions and at higher concentrations no aggregation is observed. With these results, it is possible to state that with the incorporation of a single tryptophan to the N-terminus, a highly active peptide was obtained due to the π–electron system of tryptophan, resulting in negatively charged clouds, that participate in cation–π interactions with lysine residues. Furthermore, we propose that W-BP100 action can be achieved by electrostatic interactions followed by peptide translocation.

scholarly journals Preference of Proteomonas Sulcata Anion Channelrhodopsin for Nitrate Revealed Using a pH Electrode Method

2021 ◽  
Author(s):  
Chihiro Kikuchi ◽  
Hina Kurane ◽  
Takuma Watanabe ◽  
Makoto Demura ◽  
Takashi Kikukawa ◽  
...  
Keyword(s):  
Transmembrane Helix ◽  
Anion Transport ◽  
Yeast Cells ◽  
Ion Pump ◽  
Transport Activity ◽  
Electrode Method ◽  
Anion Transport Activity ◽  
Living Organisms ◽  
Stable Forms ◽  
Ph Electrode

Abstract Ion channel proteins are physiologically important molecules in living organisms. Their molecular functions have been investigated using electrophysiological methods, which enable quantitative, precise and advanced measurements and thus require complex instruments and experienced operators. For simpler and easier measurements, we measured the anion transport activity of light-gated anion channelrhodopsins (ACRs) using a pH electrode method, which has already been established for ion pump rhodopsins. Using that method, we successfully measured the anion transport activity and its dependence on the wavelength of light, i.e. its action spectra, and on the anion species, i.e. its selectivity or preference, of several ACRs expressed in yeast cells. In addition, we identified the strong anion transport activity and the preference for NO3- of an ACR from a marine cryptophyte algae Proteomonas sulcata, named PsuACR_353. Such a preference was discovered for the first time in microbial pump- or channel-type rhodopsins. Nitrate is one of the most stable forms of nitrogen and is used as a nitrogen source by most organisms including plants. Therefore, PsuACR_353 may play a role in NO3- transport and might take part in NO3--related cellular functions in nature. Measurements of a mutant protein revealed that a Thr residue in the 3rd transmembrane helix, which corresponds to Cys102 in GtACR1, contributed to the preference for NO3-. These findings will be helpful to understand the mechanisms of anion transport, selectivity and preference of PsuACR_353.

scholarly journals Size matters: Size Dependency of Gold Nanoparticles Interacting with Model Membranes

2019 ◽  
Author(s):  
Claudia Contini ◽  
James W. Hindley ◽  
Tom Macdonald ◽  
Joseph Barritt ◽  
Oscar Ces ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Lipid Bilayers ◽  
Lipid Membrane ◽  
Rapid Development ◽  
Membrane System ◽  
Size Dependent ◽  
Research Fields ◽  
Large Unilamellar Vesicles ◽  
Wide Range ◽  
Experimental Characterisation

<p><b>The rapid development of nanomaterials has led to an increase in the number and variety of engineered nanomaterials (ENMs) in the environment. Gold nanoparticles (AuNPs) are an example of a commonly studied ENM whose highly tailorable properties have generated significant interest through a wide range of research fields. In the present work, we report the first qualitative as well as quantitative experimental characterisation of the AuNP-membrane interaction. We investigate the interactions between citrate-stabilised AuNPs (diameters 5, 10, 25, 35, 50, 60 nm) and large unilamellar vesicles (LUVs) acting as a model membrane system. LUVs were prepared in two different formulations using 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and 1,2-dileoyl-sn-glycero-3-phosphocholine (DOPC). Our results show that the interaction between AuNPs and LUVs is size dependent; in particular, we reveal the existence of two AuNP’s critical diameters which determine the fate of AuNPs in contact with a lipid membrane. The results provide a new understanding of the size dependent interaction between AuNPs and lipid bilayers of direct relevance to nanotoxicology and to the design of NP vectors.</b></p>

Ion transport mediated by copolymers composed of polyoxyethylene and polyoxypropylene

1988 ◽  
Vol 254 (1) ◽  
pp. C20-C26 ◽  
Author(s):  
T. P. Atkinson ◽  
J. O. Bullock ◽  
T. F. Smith ◽  
R. E. Mullins ◽  
R. L. Hunter
Keyword(s):  
Ion Transport ◽  
Lipid Bilayers ◽  
Practical Interest ◽  
Water Soluble ◽  
Planar Lipid Bilayers ◽  
Monovalent Cations ◽  
Transport Activity ◽  
Experimental Systems ◽  
Surface Active Agents ◽  
Surface Active

Block copolymers composed of polyoxyethylene and polyoxypropylene were found to increase the influx of Na+ and the efflux of K+ from human erythrocytes. They were, however, ineffective at promoting the transport of Ca2+. The size of the ion fluxes induced by the copolymers correlated with their efficacy in stimulating inflammation. These compounds were also found to induce conductance increases in planar lipid bilayers in a nonvoltage dependent and nonstepwise manner. In both experimental systems, ion transport was facilitated only under temperature and ionic-strength conditions in which the polymers form aggregates in aqueous solution. In neither system did the concentration dependence of transport activity exhibit a pronounced cooperativity. These observations are consistent with the view that aqueous monomers of these surface active agents partition into the membrane, where they facilitate the conductive movement of monovalent cations by means of a carrier type mechanism. As a novel class of ionophores, these substances are of practical interest because they can be water soluble and are potentially reversible.

scholarly journals Band 3 HT, a human red-cell variant associated with acanthocytosis and increased anion transport, carries the mutation Pro-868→Leu in the membrane domain of band 3

1993 ◽  
Vol 293 (2) ◽  
pp. 317-320 ◽  
Author(s):  
L J Bruce ◽  
M M Kay ◽  
C Lawrence ◽  
M J Tanner
Keyword(s):  
Cell Shape ◽  
Band 3 ◽  
Anion Transport ◽  
Red Cell ◽  
Transport Activity ◽  
Binding Properties ◽  
Red Cell Shape ◽  
Disulphonic Acid ◽  
Anion Transport Activity ◽  
Cell Variant

1. We have studied band 3 HT, a human red-cell band 3 variant with increased M(r), which is associated with abnormal red-cell shape (acanthocytosis) and increased anion-transport activity. 2. We have shown that the increased M(r) does not result from the presence of the band 3 Memphis mutation, and that the variant band 3 is covalently labelled by 4,4′-di-isothiocyanato-1,2-diphenylethane-2,2′-disulphonic acid (H2DIDS) less readily than normal. 3. cDNA cloning studies show that band 3 HT results from the mutation Pro-868-->Leu, and the possible significance of the mutation in the altered anion-transport activity and cytoskeleton binding properties of band 3 HT is discussed.

scholarly journals Engineered covalent leucotoxin heterodimers form functional pores: insights into S–F interactions

2006 ◽  
Vol 396 (2) ◽  
pp. 381-389 ◽  
Author(s):  
Olivier Joubert ◽  
Gabriella Viero ◽  
Daniel Keller ◽  
Eric Martinez ◽  
Didier A. Colin ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Pore Formation ◽  
Polymorphonuclear Neutrophils ◽  
Target Cells ◽  
Single Family ◽  
Wild Type ◽  
Subunit Interactions ◽  
Human Red Blood Cells ◽  
Large Unilamellar Vesicles ◽  
New Strategy

The staphylococcal α-toxin and bipartite leucotoxins belong to a single family of pore-forming toxins that are rich in β-strands, although the stoichiometry and electrophysiological characteristics of their pores are different. The different known structures show a common β-sandwich domain that plays a key role in subunit–subunit interactions, which could be targeted to inhibit oligomerization of these toxins. We used several cysteine mutants of both HlgA (γ-haemolysin A) and HlgB (γ-haemolysin B) to challenge 20 heterodimers linked by disulphide bridges. A new strategy was developed in order to obtain a good yield for S-S bond formation and dimer stabilization. Functions of the pores formed by 14 purified dimers were investigated on model membranes, i.e. planar lipid bilayers and large unilamellar vesicles, and on target cells, i.e. rabbit and human red blood cells and polymorphonuclear neutrophils. We observed that dimers HlgA T28C–HlgB N156C and HlgA T21C–HlgB T157C form pores with similar characteristics as the wild-type toxin, thus suggesting that the mutated residues are facing one another, allowing pore formation. Our results also confirm the octameric stoichiometry of the leucotoxin pores, as well as the parity of the two monomers in the pore. Correctly assembled heterodimers thus constitute the minimal functional unit of leucotoxins. We propose amino acids involved in interactions at one of the two interfaces for an assembled leucotoxin.

scholarly journals Chloride Transport Across Planar Lipid Bilayers and Cell Membranes by Steriod-Based Synthetic Anion Transporters

2014 ◽  
Vol 106 (2) ◽  
pp. 188a-189a ◽  
Author(s):  
Hongyu Li ◽  
Germinal Magro ◽  
Luke W. Judd ◽  
Peter R. Brotherhood ◽  
David N. Sheppard ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Cell Membranes ◽  
Chloride Transport ◽  
Planar Lipid Bilayers ◽  
Anion Transporters

Molecular and global structure and dynamics of membranes and lipid bilayers

1990 ◽  
Vol 68 (9) ◽  
pp. 999-1012 ◽  
Author(s):  
E. Sackmann
Keyword(s):  
Lipid Bilayers ◽  
Plasma Membranes ◽  
Mechanical Stability ◽  
Dynamic Properties ◽  
Composite Membranes ◽  
Two Dimensional ◽  
Molecular Architecture ◽  
Present Contribution ◽  
Cell Plasma ◽  
Low Dimensionality

The cell plasma is a composite type of material that is made up of a two-dimensional liquid crystal (lipid–protein bilayer) to which a macromolecular network (the cytoskeleton) is loosely coupled. The latter may be approximately two dimensional as in the case of the erythrocytes or may extend throughout the whole cell cytoplasm. Owing to this combination of two states of matter, the membrane combines the dynamics and flexibility of a fluid with the mechanical stability of a solid. Owing to its low dimensionality, the local structure of the bilayer or the global shape of cells may be most effectively controlled and modulated by biochemical signals such as macromolecular adsorption. The present contribution deals with comparative studies of the local and global dynamic properties of biological and artificial membranes. In the first part the question of the physical basis of selective lipid–protein interaction mechanisms is addressed and the outstanding viscoelastic properties of plasma membranes and their role for local instabilities shape fluctuations of cells and the cell–substrate interaction are described. The second part deals with the molecular architecture and dynamics of composite membranes prepared by combining monomeric and macromolecular lipids. These model membranes open new possibilities to mimick complex mechanical processes of cell plasma membranes and to prepare low-dimensionality macromolecular solutions and gels. Finally, the use of such compound systems by nature to prepare the semipermeable protective layers of plant leaves, the so-called cuticle, is discussed. In analogy to plasma membranes, the local transport properties are modulated by variation of the liquid-crystalline state of the monomeric waxes.

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