Surface plasmon resonance biosensor assay for the analysis of small-molecule inhibitor binding to human and parasitic phosphodiesterases.

M.H. Siderius, A. Shanmugham, P. England, T.K. van der Meer, J.P. Bebelman, A.R. Blaazer, I.J.P. de Esch, R. Leurs

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

In the past decade, surface plasmon resonance (SPR) biosensor-based technology has been exploited more and more to characterize the interaction between drug targets and small-molecule modulators. Here, we report the successful application of SPR methodology for the analysis of small-molecule binding to two therapeutically relevant cAMP phosphodiesterases (PDEs), Trypanosoma brucei PDEB1 which is implicated in African sleeping sickness and human PDE4D which is implicated in a plethora of disease conditions including inflammatory pulmonary disorders such as asthma, chronic obstructive pulmonary disease and central nervous system (CNS) disorders. A protocol combining the use of directed capture using His-tagged PDE-CDs with covalent attachment to the SPR surface was developed. This methodology allows the determination of the binding kinetics of small-molecule PDE inhibitors and also allows testing their specificity for the two PDEs. The SPR-based assay could serve as a technology platform for the development of highly specific and high-affinity PDE inhibitors, accelerating drug discovery processes.
LanguageEnglish
Pages41-49
JournalAnalytical Biochemistry
Volume503
DOIs
Publication statusPublished - 2016

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Surface Plasmon Resonance
Phosphoric Diester Hydrolases
Surface plasmon resonance
Biosensing Techniques
Biosensors
Assays
Molecules
Phosphodiesterase Inhibitors
Drug interactions
African Trypanosomiasis
Technology
Pulmonary diseases
Trypanosoma brucei brucei
Central Nervous System Diseases
Neurology
Drug Discovery
Drug Interactions
Chronic Obstructive Pulmonary Disease
Modulators
Asthma

Cite this

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title = "Surface plasmon resonance biosensor assay for the analysis of small-molecule inhibitor binding to human and parasitic phosphodiesterases.",
abstract = "In the past decade, surface plasmon resonance (SPR) biosensor-based technology has been exploited more and more to characterize the interaction between drug targets and small-molecule modulators. Here, we report the successful application of SPR methodology for the analysis of small-molecule binding to two therapeutically relevant cAMP phosphodiesterases (PDEs), Trypanosoma brucei PDEB1 which is implicated in African sleeping sickness and human PDE4D which is implicated in a plethora of disease conditions including inflammatory pulmonary disorders such as asthma, chronic obstructive pulmonary disease and central nervous system (CNS) disorders. A protocol combining the use of directed capture using His-tagged PDE-CDs with covalent attachment to the SPR surface was developed. This methodology allows the determination of the binding kinetics of small-molecule PDE inhibitors and also allows testing their specificity for the two PDEs. The SPR-based assay could serve as a technology platform for the development of highly specific and high-affinity PDE inhibitors, accelerating drug discovery processes.",
author = "M.H. Siderius and A. Shanmugham and P. England and {van der Meer}, T.K. and J.P. Bebelman and A.R. Blaazer and {de Esch}, I.J.P. and R. Leurs",
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language = "English",
volume = "503",
pages = "41--49",
journal = "Analytical Biochemistry",
issn = "0003-2697",
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Surface plasmon resonance biosensor assay for the analysis of small-molecule inhibitor binding to human and parasitic phosphodiesterases. / Siderius, M.H.; Shanmugham, A.; England, P.; van der Meer, T.K.; Bebelman, J.P.; Blaazer, A.R.; de Esch, I.J.P.; Leurs, R.

In: Analytical Biochemistry, Vol. 503, 2016, p. 41-49.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Shanmugham, A.

AU - England, P.

AU - van der Meer, T.K.

AU - Bebelman, J.P.

AU - Blaazer, A.R.

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AU - Leurs, R.

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AB - In the past decade, surface plasmon resonance (SPR) biosensor-based technology has been exploited more and more to characterize the interaction between drug targets and small-molecule modulators. Here, we report the successful application of SPR methodology for the analysis of small-molecule binding to two therapeutically relevant cAMP phosphodiesterases (PDEs), Trypanosoma brucei PDEB1 which is implicated in African sleeping sickness and human PDE4D which is implicated in a plethora of disease conditions including inflammatory pulmonary disorders such as asthma, chronic obstructive pulmonary disease and central nervous system (CNS) disorders. A protocol combining the use of directed capture using His-tagged PDE-CDs with covalent attachment to the SPR surface was developed. This methodology allows the determination of the binding kinetics of small-molecule PDE inhibitors and also allows testing their specificity for the two PDEs. The SPR-based assay could serve as a technology platform for the development of highly specific and high-affinity PDE inhibitors, accelerating drug discovery processes.

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