Solid-supported lipid membranes as a tool for determination of membrane affinity: High-throughput screening of a physicochemical parameter

Loidl-Stahlhofen, Angelika; Eckert, Annett; Hartmann, Thorsten; Schöttner, Matthias

doi:10.1002/1520-6017(200105)90:5<597::aid-jps1016>3.0.co;2-p

Cited by 24 publications

(39 citation statements)

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“…For every halogen atom, a certain amount is deduced from the real molecular weight (CL: j22, F: j17, Br: j62, I: j98) (7). As a lipophilicity measure, the membrane affinity MA, i. e. a partition coefficient between aqueous buffer and an immobilized lipid bilayer (12,13)] is preferred, but other more commonly used lipophilicity measures such as octanol/water partition coefficients (P) might also work, since there is a reasonable correlation between LogMA and LogP in the range of approximately 1 < LogP < 4 (14). Equation (1) accounts for passive transcellular uptake by diffusion through the membrane (left term of the right hand side) including the influence of the unstirred water layer as well as paracellular transport (right term of the right hand side) via a sigmoidal relation (7,11).…”

Section: Model Structurementioning

confidence: 99%

Development and Validation of a Physiology-based Model for the Prediction of Oral Absorption in Monkeys

2007

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Section: Model Structurementioning

confidence: 99%

Development and Validation of a Physiology-based Model for the Prediction of Oral Absorption in Monkeys

2007

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“…In our previous work [3][4][5] we have already described the first experiments for the determination of membrane affinity or HSA-Binding using 96 well filter plates. A shared feature of the assays is the titration of a constant concentration of the compound of interest (e.g.…”

Section: Resultsmentioning

confidence: 99%

“…moleculardevices.com). A further description of the materials and the detailed calculation of membrane affinity or serum protein binding is described in [3], [4] and [5].…”

Section: Introductionmentioning

confidence: 99%

ADME Related Profiling in 96 and 384 Well Plate Format - A Novel and Robust HT-Assay for the Determination of Lipophilicity and Serum Albumin Binding

Hartmann¹,

Schmitt²,

Röhring³

et al. 2006

CDD

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The failure of about half of the drug candidates is associated with poor pharmacokinetic properties leading to a huge loss of time and money [1]. Early profiling of drug like properties provides important information in order to screen out insoluble, poorly absorbed and toxic compounds. Today, large compound libraries have to be screened, and of course the total number of compounds will rise over the next years leading to a growing demand for fully automated assays. A balance between quality, speed, throughput, cost and information content can be accomplished by the careful selection of assays and experimental conditions. Here we describe a novel 384 well format assay for two important ADME related descriptors (lipophilicity and serum protein binding) as input parameters for a precise prediction of fraction absorbed, blood/organ distribution coefficients and permeability, in order to maximize the information about a compound at an early stage of discovery.

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“…The resulting solid-supported lipid membranes do not show any unspecific surface effects due to the support and can be used as affinity tools in chromatography [38] and high-throughput binding studies. [20] By increasing the space between support and lipid bilayer functional incorporation of integral membrane proteins becomes feasible. The resulting materials enable transport studies and target screening; fluorescence approaches towards fully automated set-ups are currently in progress.…”

Section: Discussionmentioning

confidence: 99%

“…Conventional experimental approaches rely on partitioning models such as octanol±water, [16,17] lipid vesicle systems, [18] IAM- [8] or BLMassays. [19] In contrast to these systems, the TRANSIL approach [20] can combine the fluidity of a true bilayer system (high physiological relevance) with a handy measurement format (short expense of time).…”

Section: Artificial Lipid Membrane Modelsmentioning

confidence: 99%

Solid-Supported Biomolecules on Modified Silica Surfaces—A Tool for Fast Physicochemical Characterization and High-Throughput Screening

Loidl-Stahlhofen¹,

Schmitt²,

Nöller³

et al. 2001

Adv. Mater.

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Biofunctionalization for a wide variety of applications can be achieved by coating silica surfaces with biomolecules such as lipids or proteins. However, specific surface optimization of the inorganic SiO2 is necessary to achieve biocompatible surfaces. Surface shielded porous silica beads can be non‐covalently coated with a single lipid bilayer. The lipids retain their fluidity in this handy solid‐supported system, perfectly mimicking the soft‐surface properties of cellular membranes. A supramolecular architecture can also be used for functional immobilization of membrane proteins: An artificial cytosolic compartment can be created with the aid of polymers; coating by lipid membranes and integration of membrane proteins results in a solid‐supported biofunctional cellular surface. Another surface modification enables a direct immobilization of human serum albumin (HSA) molecules onto silica surfaces. The HSA on this otherwise passivated surface provides a convenient material for the investigation of unspecific protein binding of pharmaceuticals on a high‐throughput scale.

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Solid-supported lipid membranes as a tool for determination of membrane affinity: High-throughput screening of a physicochemical parameter

Cited by 24 publications

References 0 publications

Development and Validation of a Physiology-based Model for the Prediction of Oral Absorption in Monkeys

Development and Validation of a Physiology-based Model for the Prediction of Oral Absorption in Monkeys

ADME Related Profiling in 96 and 384 Well Plate Format - A Novel and Robust HT-Assay for the Determination of Lipophilicity and Serum Albumin Binding

Solid-Supported Biomolecules on Modified Silica Surfaces—A Tool for Fast Physicochemical Characterization and High-Throughput Screening

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