Membrane Transporters for Anions That Use a Relay Mechanism

McNally, Beth A.; O’Neil, Edward; Nguyen, Anh Thi Van; Smith, Bradley D.

doi:10.1021/ja8082363

Cited by 62 publications

(58 citation statements)

References 18 publications

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“…11 Other developments include for example a novel "relay" mechanism, wherein an ion transported by 7 is passed on from a synthetic transporter on one side of the membrane to another transporter on the opposite site. 12 Particularly rewarding development may be the interaction of transition metals with organic ligands directing the self-assembly of synthetic ion channels and pores such as in 8 and 9, 13,14 the use of bioinspired motifs such as G-quartets in 10, 15 and applications in artificial photosystems 4 or 9, 9,14 or to living cells. 7 Herein, we mainly use the general term "synthetic transport systems" for systems which facilitate transport of ions / molecules across bilayer membranes by any mechanism except simple membrane disruption by detergents.…”

Section: Introductionmentioning

confidence: 99%

Transport Experiments in Membranes

Matile¹,

Sakai²,

Hennig³

2012

Supramolecular Chemistry

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In this contribution, we describe methods to characterize the activity of synthetic transport systems in translocating molecules across otherwise impermeable membranes. The first two sections introduce methods with bulk membranes (U-tube experiments) and planar or "black" lipid membranes (BLMs), and close with a more comprehensive overview of methods involving liposomes, in particular large unilamellar vesicles (LUVs). The fourth section focuses on the application of these methods to the elucidation of the functional characteristics of synthetic transport systems. This includes sensitivity toward membrane composition, membrane potential, pH, anions, cations, molecular recognition (sensing), molecular transformation (catalysis) or light (photosynthesis).

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Section: Introductionmentioning

confidence: 99%

Transport Experiments in Membranes

Matile¹,

Sakai²,

Hennig³

2012

Supramolecular Chemistry

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“…Environmental toxins can also enter the human body by passively crossing cell membranes 3–6. Understanding the mechanistic details of passive transport is essential to understanding how and why certain molecules make good drugs or dangerous toxins, and can further help design suitable drugs 7–8…”

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confidence: 99%

Confocal Imaging to Quantify Passive Transport across Biomimetic Lipid Membranes

Malmstadt

2010

Anal. Chem.

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The ability of a molecule to pass through the plasma membrane without the aid of any active cellular mechanisms is central to that molecule's pharmaceutical characteristics. Passive transport has been understood in the context of Overton's rule, which states that more lipophilic molecules cross membrane lipid bilayers more readily. Existing techniques for measuring passive transport lack reproducibility and are hampered by the presence of an unstirred layer (USL) that dominates transport across the bilayer. This report describes assays based on spinning-disk confocal microscopy (SDCM) of giant unilamellar vesicles (GUVs) that allow for the detailed investigation of passive transport processes and mechanisms. This approach allows the concentration field to be directly observed, allowing membrane permeability to be determined easily from the transient concentration profile data. A series of molecules of increasing hydrophilicity was constructed and the transport of these molecules into GUVs was observed. The observed permeability trend is consistent with Overton's rule. However, the values measured depart from the simple partitiondiffusion proportionality model of passive transport. This technique is easy to implement and has great promise as an approach to measure membrane transport. It is optimally suited to precise quantitative measurements of the dependence of passive transport on membrane properties. KeywordsConfocal microscope; giant unilamellar vesicle; passive membrane transport Passive transport through the cell membrane represents a major route by which drugs enter cells. It is the primary route by which orally delivered drugs enter systemic circulation. [1][2] Environmental toxins can also enter the human body by passively crossing cell membranes. [3][4][5][6] Understanding the mechanistic details of passive transport is essential to understanding how and why certain molecules make good drugs or dangerous toxins, and can further help design suitable drugs. [7][8] For over a century, the passive transport of small molecules through lipid bilayers has been understood in the context of Overton's rule, which broadly states that more lipophilic molecules cross bilayers more readily. 9 More precisely, the consensus holds that membrane permeability is proportional to the product of the molecular diffusivity D and the oil-water partition coefficient K of the permeating species. Since K is expected to vary more than D for small drug-like molecules, oil-water partition coefficients have been widely used to estimate membrane permeability. [10][11][12] malmstad@usc.edu. [19][20][21] Studies using the pharmaceutical industry-standard parallel artificial membrane permeability assay (PAMPA), the most common planar bilayer approach, have reported a wide range of permeabilities for drugs such as propranolol and testosterone. 22 Another example of the lack of reproducibility in membrane permeation assays was recently presented by Grime and coworkers, who described the wide range of reported permeabilities for we...

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“…Smith and co-workers have functionalised lipids with anion binding urea groups (44 and 45) and also prepared a control compound that has a very low affinity for chloride (46) [31]. Compounds 44 and 45 act as chloride transporters via a relay mechanism wherein the anion is complexed by the urea of a lipid in one leaflet of the membrane and transported to the centre of the bilayer where it is handed to a functionalised lipid in the other leaflet.…”

Section: Anion Transport Across Lipid Bilayersmentioning

confidence: 99%