Analysis of ligand binding by bioaffinity mass spectrometry

Zhu, Yusheng; Valdes, Roland; Simmons, Christine Q.; Linder, Mark W.; Pugia, Michael J.; Jortani, Saeed A.

doi:10.1016/j.cca.2006.02.023

Cited by 7 publications

(6 citation statements)

References 21 publications

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“…Detection of captured compounds, e.g. target proteins, can be obtained in different ways: (i) by total labeling of the analyzed sample, (ii) an additional, secondary, affinity reagent may be used or (iii) label free detection could be achieved by methods as surface plasmon resonance (SPR) (Seitz et al, 2006) or surface enhanced laser desorption ionization-time of flight mass spectrometry (SELDI) (Zhu et al, 2006). (B) Reverse phase arrays consist of spotted analytes.…”

Section: Discussionmentioning

confidence: 99%

Approaches for systematic proteome exploration

Falk

Ramström

Ståhl

et al. 2007

Biomolecular Engineering

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Section: Discussionmentioning

confidence: 99%

Approaches for systematic proteome exploration

Falk

Ramström

Ståhl

et al. 2007

Biomolecular Engineering

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“…Indirect methods that are available to measure K d values and, thus, van't Hoff enthalpies in this way include spectroscopic methods such as surface plasmon resonance [29][30][31] , NMR [32] and mass spectrometry [33] , chromatographic methods including frontal affinity chromatography [34] and capillary electrophoresis [35] , as well as standard methods, such as radioligand binding. A detailed description of each of these methods is beyond the scope of this review, but a generalisation of the method for determination of enthalpy by these indirect approaches is given briefly below.…”

Section: Indirect Thermodynamic Measurementsmentioning

confidence: 99%

Thermodynamics of binding interactions in the rational drug design process

Holdgate

2007

Expert Opinion on Drug Discovery

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Modern drug discovery usually involves the rapid screening of large numbers of compounds, either individually or in resolvable mixtures. These compounds may be complex and lead-like or may be small fragments representing optimal scaffolds. Several methods are suitable for detecting binding interactions based on a wide range of different physical platforms. However, the use of thermodynamic measurements has a role to play both in the high-throughput identification of binders and also in the fundamental understanding of molecular interaction, which is central to rational drug design. This review describes the benefits and drawbacks of using thermodynamic characterisation of binding interactions at various stages in the rational drug design process and highlights future opportunities for advances in instrumentation and methodology.

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“…Using a mouse model of APAP toxicity established in our laboratory [28], we hypothesized that animals pretreated with low doses of this drug prior to a final toxic dose differentially express proteins compared to naïve animals and, as such, these proteins may contribute to the observed hepatoprotection in our model system. Understanding the mechanisms for adaptive tolerance to drugs may provide insights into better diagnoses and treatments for drug toxicities.…”

Section: Introductionmentioning

confidence: 99%

“…Recent technological advancements in proteomic profiling and bioinformatics have allowed for a dramatic increase in the analyses of biomarkers in complex biological fluids including: serum and plasma [16][17][18][19], urine [20][21][22][23], cellular subfractions [24][25][26], ligand binding [27][28][29], and cerebral spinal fluid [30,31]. Although these applications have systematic limitations [32][33][34], a variety of platforms are being used for the separation and identification of novel proteins involved in various cellular processes.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Study of Hepatic Nuclear Extracts in an Adaptive Acetaminophen Tolerance Model

et al. 2009

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Introduction Variability in response to acetaminophen (APAP)-induced aseptic inflammation and tolerance to the impending hepatic damage has been described. To understand the mechanism of adaptive tolerance, we investigated the proteomic profiles of crude nuclear lysates in a mouse model. We hypothesized that pretreatment with low doses of APAP prior to a toxic dose results in differential protein expression. Materials and Methods Mice (BALB/C) were separated into three groups: the pretreated (PT) group received incremental doses of APAP while the last dose only (LD) and naïve groups were given saline vehicle. A toxic dose of APAP was administered on the seventh day to the PT and LD animals only and all groups were euthanized 3 h postdose. Total protein from crude hepatic nuclear lysates were applied to protein arrays and analyzed by immunoaffinity mass spectrometry. Results and Discussion Comparative data analyses of protein peaks revealed a protein that was significantly increased at m/z of 60,030 (p60) in the LD animals vs the other two groups. The closest match for the preliminary identification of the p60 protein based on a Swiss-Prot/ TagIdent database search using the approximate isoelectric point and molecular weight information was Ccr4-Not complex subunit-2. This protein is a subunit of a multiprotein complex and serves as a transcriptional suppressor involved in controlling mRNA synthesis and degradation.Preliminary identification was also supported by Western blot analysis using anti-CNOT2 antibody. Conclusion Considering the APAP tolerance model, we conclude that toxicogenomic approaches such as nuclear profiling are useful tools in assessing differential expression of transcriptional factors involved in inflammatory response and adaptive tolerance to toxins.

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Analysis of ligand binding by bioaffinity mass spectrometry

Cited by 7 publications

References 21 publications

Approaches for systematic proteome exploration

Approaches for systematic proteome exploration

Thermodynamics of binding interactions in the rational drug design process

Proteomic Study of Hepatic Nuclear Extracts in an Adaptive Acetaminophen Tolerance Model

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