A5083900205- Click Chemistry and Applications
- Protein Degradation and Inhibitors
- Computational Drug Discovery Methods
- Coastal wetland ecosystem dynamics
- Ubiquitin and proteasome pathways
- Metabolomics and Mass Spectrometry Studies
- Chemical Synthesis and Analysis
- Cancer-related Molecular Pathways
- Peatlands and Wetlands Ecology
- Peptidase Inhibition and Analysis
- Innovative Microfluidic and Catalytic Techniques Innovation
- Coastal and Marine Dynamics
- Histone Deacetylase Inhibitors Research
- Advanced Breast Cancer Therapies
- Aeolian processes and effects
- Machine Learning in Materials Science
- Marine and coastal plant biology
- Botany and Plant Ecology Studies
- vaccines and immunoinformatics approaches
- Analytical Chemistry and Chromatography
- Advanced biosensing and bioanalysis techniques
- Bioinformatics and Genomic Networks
- bioluminescence and chemiluminescence research
- Chemistry and Chemical Engineering
- CRISPR and Genetic Engineering
University of Strathclyde
2016-2023
Age UK
2023
GlaxoSmithKline (United Kingdom)
2014-2021
Bord na Móna (Ireland)
2016-2018
New York State Department of Environmental Conservation
2002
Drained peat soils are a significant source of greenhouse gas (GHG) emissions to the atmosphere. Rewetting these is considered an important climate change mitigation tool reduce and create suitable conditions for carbon sequestration. Long-term monitoring essential capture interannual variations in GHG associated environmental variables uncertainty linked with emission factor calculations. In this study, we present balances: dioxide (CO2 ), methane (CH4 ) nitrous oxide (N2 O) calculated...
The BRPF (bromodomain and PHD finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. Here, we report the discovery, binding mode, structure-activity relationship (SAR) first potent, selective series inhibitors BRPF1 bromodomain.
Advances in genomic analyses enable the identification of new proteins that are associated with disease. To validate these targets, tool molecules required to demonstrate a ligand can have disease-modifying effect. Currently, as tools reported for only fraction proteome, platforms discovery essential leverage insights from analyses. Fragment screening offers an efficient approach explore chemical space. Presented here is fragment-screening platform, termed PhABits (PhotoAffinity Bits), which...
Methods for rapid identification of chemical tools are essential the validation emerging targets and to provide medicinal chemistry starting points development new medicines. Here, we report a screening platform that combines 'direct-to-biology' high-throughput (D2B-HTC) with photoreactive fragments. The enabled synthesis >1000 PhotoAffinity Bits (HTC-PhABits) in 384-well plates 24 h their subsequent as crude reaction products protein target without purification. Screening HTC-PhABit library...
The BRPF (Bromodomain and PHD Finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. A selective benzimidazolone BRPF1 inhibitor showing micromolar activity in a cellular target engagement assay was recently described. Herein, we report the optimization this series leading to identification superior suitable vivo studies.
Abstract The CDK family plays a crucial role in the control of cell cycle. Dysregulation and mutation CDKs has been implicated cancer have investigated extensively as potential therapeutic targets. Selective inhibition specific isoforms is to achieve effect while minimising toxicity. We present group photoaffinity probes designed bind CDKs. site crosslinking optimised probe, well its ability enrich members from lysates, was investigated. In proof concept study, we subsequently developed...
We demonstrate that PyParse, an open-access tool, improves upon existing methods for analysis of LC-MS data obtained high-throughput experimentation.
Reactive fragment (RF) screening has emerged as an efficient method for ligand discovery across the proteome, irrespective of a target’s perceived tractability. To date, however, efficiency subsequent optimisation campaigns largely been low‐throughput, constrained by need synthesis and purification target compounds. We report high‐throughput platform ‘direct‐to‐biology’ (D2B) cysteine‐targeting chloroacetamide RFs, wherein is performed in 384‐well plates allowing direct assessment downstream...
We present a one-step Ugi reaction protocol for the expedient synthesis of photoaffinity probes live-cell MS-based proteomics. The couples an amine affinity function with commonly used photoreactive groups, and variety handle functionalities. Using this technology, series pan-BET (BET: bromodomain extra-terminal domain) selective were obtained by parallel synthesis. Studies on effects group, linker length irradiation wavelength photocrosslinking efficiency provide valuable insights into...
Abstract Advances in genomic analyses enable the identification of new proteins that are associated with disease. To validate these targets, tool molecules required to demonstrate a ligand can have disease‐modifying effect. Currently, as tools reported for only fraction proteome, platforms discovery essential leverage insights from analyses. Fragment screening offers an efficient approach explore chemical space. Presented here is fragment‐screening platform, termed PhABits (PhotoAffinity...
<p>Methods for rapid identification of chemical tools are essential the validation emerging targets and to provide medicinal chemistry starting points development <a>new medicines. Here, we report a screening platform that combines ‘direct-to-biology’ high-throughput (D2B-HTC) with photoreactive covalent fragments. The enabled synthesis >1000 PhotoAffinity Bits (HTC-PhABits) in 384-well plates. Screening HTC-PhABit library </a>carbonic anhydrase I (CAI) afforded 7 hits...
Abstract The CDK family plays a crucial role in the control of cell cycle. Dysregulation and mutation CDKs has been implicated cancer have investigated extensively as potential therapeutic targets. Selective inhibition specific isoforms is to achieve effect while minimising toxicity. We present group photoaffinity probes designed bind CDKs. site crosslinking optimised probe, well its ability enrich members from lysates, was investigated. In proof concept study, we subsequently developed...
High-throughput experimentation for chemistry and chemical biology has emerged as a highly impactful technology, particularly when applied to Direct-to-Biology. Analysis of the rich datasets which come from this mode continues be rate-limiting step reaction optimisation submission compounds biological assay. We present PyParse, an automated, accurate accessible program data extraction high-throughput provide real-life examples situations in PyParse can dramatic improvements speed accuracy...
Reactive fragment (RF) screening has emerged as an efficient method for ligand discovery across the proteome, irrespective of a target’s perceived tractability. To date, however, efficiency subsequent optimisation campaigns largely been low-throughput, constrained by need synthesis and purification target compounds. We report high-throughput platform ‘direct-to-biology’ (D2B) cysteine-targeting chloroacetamide RFs, wherein is performed in 384-well plates allowing direct assessment downstream...
Reactive fragment (RF) screening has emerged as an efficient method for ligand discovery across the proteome, irrespective of a target’s perceived tractability. To date, however, efficiency subsequent optimisation campaigns largely been low‐throughput, constrained by need synthesis and purification target compounds. We report high‐throughput platform ‘direct‐to‐biology’ (D2B) cysteine‐targeting chloroacetamide RFs, wherein is performed in 384‐well plates allowing direct assessment downstream...
Advances in genomic analyses enable the identification of new proteins that are associated with disease. To validate these targets, tool molecules required to demonstrate a ligand can have disease-modifying effect. Currently, as tools reported for only fraction proteome, platforms discovery essential leverage insights from analyses. Fragment screening offers an efficient approach explore chemical space, however, it remains challenging develop techniques both sufficiently high-throughput and...
The development and optimisation of a photoaffinity labelling (PAL) displacement assay is presented, where highly efficient PAL probe was used to report on the relative binding affinities compounds specific sites in multiple recombinant protein domains tandem. N- C-terminal bromodomains BRD4 were as example target proteins. A test set 264 annotated with activity against bromodomain extra-terminal domain (BET) family ChEMBL benchmark assay. pIC50 values obtained from correlated well...
Photoaffinitätssonden wurden gezielt darauf entwickelt, cyclinabhängige Kinasen (CDKs) anzusteuern, die als Zeitnehmer zellulärer Prozesse angesehen werden können. Wie J. T. Bush und Mitarbeiter in ihrem Forschungsartikel auf S. 17483 berichten, reichern diese Sonden CDKs aus Zelllysaten kompetitiv an. Ein biochemischer Photoaffinitätsverdrängungstest wurde zur Messung der Wirkstoffpotenz entwickelt. Die im Titelbild gezeichnete Wippe stellt das konkurrierende Gleichgewicht zwischen...
Methods for rapid identification of chemical tools are essential the validation emerging targets and to provide medicinal chemistry starting points development new medicines. Here, we report a screening platform that combines ‘direct-to-biology’ high-throughput (D2B-HTC) with photoreactive covalent fragments. The enabled synthesis >1000 PhotoAffinity Bits (HTC-PhABits) in 384-well plates. Screening HTC-PhABit library carbonic anhydrase I (CAI) afforded 7 hits (0.7% hit rate), which were...