Chemical microarrays, fragment diversity, label-free imaging by plasmon resonance?a chemical genomics approach

Vetter, Dirk

doi:10.1002/jcb.10408

Cited by 28 publications

(15 citation statements)

References 29 publications

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“…In fact, they work not only as a labeler but also as a simple amplifier because of the interaction with evanescent wave onto the surface [85–87]. We make a comparison between the following examples focusing on the sensitivity, the modification, and the class of biomarker.…”

Section: Nanomodified Spr-abbs Applications For In Vitro Diagnosticsmentioning

confidence: 99%

Nanotechnology-Based Surface Plasmon Resonance Affinity Biosensors forIn VitroDiagnostics

Antiochia

Bollella

Favero

et al. 2016

International Journal of Analytical Chemistry

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In the last decades, in vitro diagnostic devices (IVDDs) became a very important tool in medicine for an early and correct diagnosis, a proper screening of targeted population, and also assessing the efficiency of a specific therapy. In this review, the most recent developments regarding different configurations of surface plasmon resonance affinity biosensors modified by using several nanostructured materials for in vitro diagnostics are critically discussed. Both assembly and performances of the IVDDs tested in biological samples are reported and compared.

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Section: Nanomodified Spr-abbs Applications For In Vitro Diagnosticsmentioning

confidence: 99%

Nanotechnology-Based Surface Plasmon Resonance Affinity Biosensors forIn VitroDiagnostics

Antiochia

Bollella

Favero

et al. 2016

International Journal of Analytical Chemistry

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“…7 Only a limited number of chemical scaffolds have been linked on microarrays for binding-based screening. 8 Given the large size and number of existing chemical libraries, no universal linkage is feasible. Houseman et al 9 advanced the use of microarrays for kinase screening by linking peptide substrates on the surface of microarray and then spotting a mixture, including chemical compound, kinase, and ATP, on top of the coating.…”

mentioning

confidence: 99%

Microarrays for the Functional Analysis of the Chemical-Kinase Interactome

Horiuchi¹,

Wang²,

Diamond³

et al. 2006

SLAS Discovery

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A central challenge in chemical biology is profiling the activity of a large number of chemical structures against hundreds of biological targets, such as kinases. Conventional 32 P-incorporation or immunoassay of phosphorylated residues produces high-quality signals for monitoring kinase reactions but is difficult to use in high-throughput screening (HTS) because of cost and the need for well-plate washing. The authors report a method for densely archiving compounds in nanodroplets on peptide or protein substrate-coated microarrays for subsequent profiling by aerosol deposition of kinases. Each microarray contains over 6000 reaction centers (1.0 nL each) whose phosphorylation progress can be detected by immunofluorescence. For p60 c-src , the microarray produced a signal-to-background ratio of 36.3 and Z′ factor of 0.63 for HTS and accurate enzyme kinetic parameters (K m ATP = 3.3 µM) and IC 50 values for staurosporine (210 nM) and PP2 (326 nM) at 10 µM adenosine triphosphate (ATP). Similarly, B-Raf phosphorylation of MEK-coated microarrays was inhibited in the nanoliter reactions by GW5074 at the expected IC 50 of 9 nM. Common kinase inhibitors were printed on microarrays, and their inhibitory activities were systematically profiled against B-Raf (V599E), KDR, Met, Flt-3 (D835Y), Lyn, EGFR, PDGFRβ, and Tie2. All results indicate that this platform is well suited for kinetic analysis, HTS, large-scale IC 50 determinations, and selectivity profiling. (Journal of Biomolecular Screening 2006:48-56)

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“…Graffinity has developed high density chemical microarrays for fragment screening consisting of small molecules immobilized onto gold chips based on maleimide-thiol coupling chemistry in combination with high density pintool spotting [78,79]. The array preparation is a three-step process consisting of the synthesis of tagged fragments, preparation of SAM-Gold chips, and covalent coupling of tagged fragments to the activated SAM surface by pintool spotting.…”

Section: High Throughput Spr Screening Of Chemical Microarraysmentioning

confidence: 99%

“…Thus, the sensitivity and detection limit of Graffinity´s SPR imager technology (PlasmonImager), allows even small protein targets to be conveniently screened with a good signal/noise ratio. SPR imaging enables a parallel readout of thousands of fragment ligands against one target simultaneously [78,79].…”

Section: High Throughput Spr Screening Of Chemical Microarraysmentioning

confidence: 99%

SPR-based Fragment Screening: Advantages and Applications

Neumann¹,

Hd²,

Schmidt³

et al. 2007

CTMC

167

100

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Fragment-based screening has recently evolved into a promising strategy in drug discovery, and a range of biophysical methods can be employed for fragment library screening. Relevant approaches, such as X-ray, NMR and tethering are briefly introduced focussing on their suitability for fragment-based drug discovery. In particular the application of surface plasmon resonance (SPR) techniques to the primary screening of large libraries comprising small molecules is discussed in detail. SPR is known to be a powerful tool for studying biomolecular interactions in a sensitive and label-free detection format. Advantages of SPR methods over more traditional assay formats are discussed and the application of available channel and array based SPR systems to biosensing are reviewed. Today, SPR protocols have been applied to secondary screening of compound libraries and hit conformation, but primary screening of large fragment libraries for drug discovery is often hampered by the throughput of available systems. Chemical microarrays, in combination with SPR imaging, can simultaneously generate affinity data for protein targets with up to 9,216 immobilized fragments per array. This approach has proven to be suitable for screening fragment libraries of up to 110,000 compounds in a high throughput fashion. The design of fragment libraries and appropriate immobilization chemistries are discussed, as well as suitable follow-up strategies for fragment hit optimization. Finally, described case studies demonstrate the successful identification of selective low molecular weight inhibitors for pharmacologically relevant drug targets through the SPR screening of fragment libraries.

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Chemical microarrays, fragment diversity, label-free imaging by plasmon resonance?a chemical genomics approach

Cited by 28 publications

References 29 publications

Nanotechnology-Based Surface Plasmon Resonance Affinity Biosensors forIn VitroDiagnostics

Nanotechnology-Based Surface Plasmon Resonance Affinity Biosensors forIn VitroDiagnostics

Microarrays for the Functional Analysis of the Chemical-Kinase Interactome

SPR-based Fragment Screening: Advantages and Applications

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