Recent advances in chromatographic and electrophoretic methods for the study of drug-protein interactions

Hage, David S.; Tweed, Stacey A.

doi:10.1016/s0378-4347(97)00178-3

Cited by 180 publications

(238 citation statements)

References 139 publications

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“…The goal of this work is to study the binding of these metabolites to HSA by using high performance affi nity chromatography and columns containing immobilized HSA. Numerous reports using HPLC-based HSA columns have reported drug-binding properties that show good agreement with those seen for soluble HSA [7,14,15]; this includes the recent work performed with phenytoin in Reference [7].…”

Section: Introductionmentioning

confidence: 56%

Studies by biointeraction chromatography of binding by phenytoin metabolites to human serum albumin

Ohnmacht

Chen

Tong

et al. 2006

Journal of Chromatography B

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Section: Introductionmentioning

confidence: 56%

Studies by biointeraction chromatography of binding by phenytoin metabolites to human serum albumin

Ohnmacht

Chen

Tong

et al. 2006

Journal of Chromatography B

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“…These methods provide information on the amount of compound bound to total plasma protein, but they do not identify the specific target. Drug binding to isolated or recombinant plasma proteins can be characterized by numerous methods such as fluorescence (58), NMR (59), CD or related spectroscopies (60), chromatography (61,62), calorimetry (37), or surface plasmon resonance (63). While these methods provide the binding affinity to the suspected plasma protein target, typically albumin for acidic drugs, or ␣ 1 -acid glycoprotein for basic drugs (64), they do not predict the extent of binding in a biological fluid because the competitive proteins and small molecules are generally unknown.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the binding selectivity of transthyretin amyloid fibril inhibitors in blood plasma

Purkey

Dorrell²

2001

Proc. Natl. Acad. Sci. U.S.A.

107

164

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Transthyretin (TTR) tetramer dissociation and misfolding facilitate assembly into amyloid fibrils that putatively cause senile systemic amyloidosis and familial amyloid polyneuropathy. We have previously discovered more than 50 small molecules that bind to and stabilize tetrameric TTR, inhibiting amyloid fibril formation in vitro. A method is presented here to evaluate the binding selectivity of these inhibitors to TTR in human plasma, a complex biological fluid composed of more than 60 proteins and numerous small molecules. Our immunoprecipitation approach isolates TTR and bound small molecules from a biological fluid such as plasma, and quantifies the amount of small molecules bound to the protein by HPLC analysis. This approach demonstrates that only a small subset of the inhibitors that saturate the TTR binding sites in vitro do so in plasma. These selective inhibitors can now be tested in animal models of TTR amyloid disease to probe the validity of the amyloid hypothesis. This method could be easily extended to evaluate small molecule binding selectivity to any protein in a given biological fluid without the necessity of determining or guessing which other protein components may be competitors. This is a central issue to understanding the distribution, metabolism, activity, and toxicity of potential drugs.

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“…Volumes of sample applied to columns in these early studies were in the range of 10-20 mL [19,20,22,23] but Shibukawa and co-workers [24][25][26][27] developed a high-performance FA format based on internal surface reversed-phase (ISRP) "restricted access"-type columns allowing the sample volume to be significantly reduced (typically 100 mL-2 mL). The use of frontal analysis in chromatographic settings has been reviewed [3,5,21,[28][29][30]. The main area of application has been drug-plasma protein binding studies.…”

Section: Frontal Analysis Methodologiesmentioning

confidence: 99%

Capillary electrophoresis frontal analysis: Principles and applications for the study of drug‐plasma protein binding

2003

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Capillary electrophoresis frontal analysis: Principles and applications for the study of drug-plasma protein bindingCapillary electrophoresis is a well-established technique for the study of noncovalent interactions. Various approaches exist and capillary electrophoresis-frontal analysis provides an interesting alternative to the migration shift affinity capillary electrophoresis methods and conventional methods. The present work reviews the principles on which the frontal analysis method is founded. Advantages and limitations of capillary electrophoresis frontal analysis in comparison with both conventional and other capillary electrophoresis based methods for quantification of binding interactions are discussed. Investigations utilizing capillary electrophoresis-frontal analysis have focused on the interaction of drugs with plasma proteins. These studies, primarily addressing the binding of drugs to human serum albumin, a 1 -acid glycoprotein, and lipoproteins are reviewed together with some recent developments in capillary electrophoresisfrontal analysis methodology.

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Recent advances in chromatographic and electrophoretic methods for the study of drug-protein interactions

Cited by 180 publications

References 139 publications

Studies by biointeraction chromatography of binding by phenytoin metabolites to human serum albumin

Studies by biointeraction chromatography of binding by phenytoin metabolites to human serum albumin

Evaluating the binding selectivity of transthyretin amyloid fibril inhibitors in blood plasma

Capillary electrophoresis frontal analysis: Principles and applications for the study of drug‐plasma protein binding

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