Recent developments in protein–ligand affinity mass spectrometry

Jonker, Niels; Kool, Jeroen; Irth, H.; Niessen, W.M.A.

doi:10.1007/s00216-010-4350-z

Cited by 80 publications

(51 citation statements)

References 96 publications

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“…As is illustrated in Fig. 3(a and b), it is also possible with zonal elution to obtain information on site-specific interactions, on the competition of two targets for the same binding agent [109,113,114] or on the competition of two binding agents to the same target [115]. As will be demonstrated in the next few sections, this format can also provide information on the strength of binding and the effects that changes in the structure of a target or binding agent may have on an interaction.…”

Section: Zonal Elution and Affinity Microcolumnsmentioning

confidence: 99%

Analysis of biomolecular interactions using affinity microcolumns: A review

Zheng

Zhao

Beeram

et al. 2014

Journal of Chromatography B

109

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Affinity chromatography has become an important tool for characterizing biomolecular interactions. The use of affinity microcolumns, which contain immobilized binding agents and have volumes in the mid-to-low microliter range, has received particular attention in recent years. Potential advantages of affinity microcolumns include the many analysis and detection formats that can be used with these columns, as well as the need for only small amounts of supports and immobilized binding agents. This review examines how affinity microcolumns have been used to examine biomolecular interactions. Both capillary-based microcolumns and short microcolumns are considered. The use of affinity microcolumns with zonal elution and frontal analysis methods are discussed. The techniques of peak decay analysis, ultrafast affinity extraction, split-peak analysis, and band-broadening studies are also explored. The principles of these methods are examined and various applications are provided to illustrate the use of these methods with affinity microcolumns. It is shown how these techniques can be utilized to provide information on the binding strength and kinetics of an interaction, as well as on the number and types of binding sites. It is further demonstrated how information on competition or displacement effects can be obtained by these methods.

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Section: Zonal Elution and Affinity Microcolumnsmentioning

confidence: 99%

Analysis of biomolecular interactions using affinity microcolumns: A review

Zheng

Zhao

Beeram

et al. 2014

Journal of Chromatography B

109

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“…Mass spectrometry (MS) is a natural label-free analytical technique that can be used for measuring protein-ligand interactions in high-throughput screenings [15,16]. Many studies have reported that traditional optical detection methods can be replaced by MS for the screening of protein or small molecule microarrays [17,18].…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Screening of the Binding of Small Molecules to Proteins by Desorption Electrospray Ionization Mass Spectrometry Combined with Protein Microarray

Yao

Wang

Zhang

et al. 2015

J. Am. Soc. Mass Spectrom.

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Abstract. The interaction between bioactive small molecule ligands and proteins is one of the important research areas in proteomics. Herein, a simple and rapid method is established to screen small ligands that bind to proteins. We designed an agarose slide to immobilize different proteins. The protein microarrays were allowed to interact with different small ligands, and after washing, the microarrays were screened by desorption electrospray ionization mass spectrometry (DESI MS). This method can be applied to screen specific protein binding ligands and was shown for seven proteins and 34 known ligands for these proteins. In addition, a high-throughput screening was achieved, with the analysis requiring approximately 4 s for one sample spot. We then applied this method to determine the binding between the important protein matrix metalloproteinase-9 (MMP-9) and 88 small compounds. The molecular docking results confirmed the MS results, demonstrating that this method is suitable for the rapid and accurate screening of ligands binding to proteins.

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“…In the latter technology either the target or the test compound is immobilized on a surface, and the interaction takes place in a flow-based or static measurement. A well-described example of the former methodology is frontal affinity chromatography or "dynamic protein affinity selection mass spectrometry" [175]. In the most common setup, the target protein is immobilized on the HPlC column material [176], while ligands flow through and bind to the target on the basis of their affinity.…”

Section: Target-ligand Screening Assaysmentioning

confidence: 99%

MS Applications in Support of Medicinal Chemistry Sciences

Honing¹,

Ingelse²,

Pramanik³

2013

Mass Spectrometry for Drug Discovery and Drug Development

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In the drug discovery process, medicinal chemistry plays a crucial role in the optimal design and synthesis (production) of new chemical entities (NCEs) or new biological entities (NBEs); this is true for a single entity as well as a complete compound library. A key requirement in this field of science is the optimization of both the chemical and the biological properties of these potential drug-like compounds. Important criteria are the design of efficient synthesis routes, the balancing of the physical chemical properties with optimal in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) processes, and a profound understanding of the pharmacodynamics in the appropriate pharmacological models. In the lead optimization stage, an important step is scaling up the synthesis route as needed for the execution of toxicology studies and the screening of suitable drug formulations. In summary, medicinal chemistry support includes participating in a large variety of activities and decision making processes that play a key role in the search for either a "first in class" new drug or a "best in class" new drug [1].These "drug discovery" processes are continuously under pressure, as the research and development (R&D) costs continue to increase and more data are requested before new drug candidates are taken into (pre-)clinical development. Hence, the choice of "targeted" high-throughput screening (HTS) libraries, the process of hit appraisal, and the understanding of target-ligand interactions can be considered the starting points for a new drug discovery program [2]. Next, the main focus is on the discovery of a lead compound; typically, this is a compound showing promising data regarding target affinity, reasonable efficacy in cellular models, good physical chemical parameters (i.e., a "drug-like" compound), and acceptable oral bioavailability in Mass Spectrometry for Drug Discovery and Drug Development, First Edition. Edited by Walter A. Korfmacher.

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Recent developments in protein–ligand affinity mass spectrometry

Cited by 80 publications

References 96 publications

Analysis of biomolecular interactions using affinity microcolumns: A review

Analysis of biomolecular interactions using affinity microcolumns: A review

Screening of the Binding of Small Molecules to Proteins by Desorption Electrospray Ionization Mass Spectrometry Combined with Protein Microarray

MS Applications in Support of Medicinal Chemistry Sciences

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