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(1 - 5 of 5)
Inhibitors and probes targeting endo-glycosidases
Boer, C. de 2021
Inhibitors and probes targeting endo-glycosidases
Doctoral Thesis
open access
2022-08-11T00:00:00Z; 2022-08-11T00:00:00Z
The chemical synthesis of inhibitors and probes targeting endo-glycosidases. 
Visualization of vitamin A metabolism
Koenders, S.T.A. 2020
Visualization of vitamin A metabolism
Doctoral Thesis
open access
2021-09-18T00:00:00Z; 2020-09-18T00:00:00Z; 2020-09-18T00:00:00Z; 2020-09-18T00:00:00Z; 2020-09-18T00:00:00Z; 2020-09-18T00:00:00Z; 2020-09-18T00:00:00Z; 2020-09-18T00:00:00Z; 2021-09-18T00:00:00Z; 2021-09-18T00:00:00Z; 2020-09-18T00:00:00Z; 2020-09-18T00:00:00Z; 2020-09-18T00:00:00Z; 2020-09-18T00:00:00Z; 2020-09-18T00:00:00Z
Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system. Vitamin A is converted to retinoic acid (RA) by aldehyde dehydrogenases (ALDHs). The family of... Show moreVitamin A or retinol is essential in embryonic development, the visual cycle and the immune system. Vitamin A is converted to retinoic acid (RA) by aldehyde dehydrogenases (ALDHs). The family of ALDHs consists of 19 members, three of which (ALDH1A1, ALDH1A2 andALDH1A3) have retinal as their preferred substrate. Due to a lack of selective and potent inhibitors for these enzymes, it is difficult to study their individual contribution to Vitamin A metabolism in biological systems.Therefore an activity-based probe based on the chemical structure of retinal has been synthesized to enable activity-based protein profiling (ABPP) of ALDHs. The probe covalently binds to the catalytic cysteine of ALDH enzymes which can then be visualized on gel or analyzed by proteomics using ligation chemistry.After biological evaluation of the probe this chemical tool has been used to study the influence of individual ALDH enzymes on the mucosal immune system and to determine the ALDH profile of several breast cancer cell lines. Thus showcasing its use to study Vitamin A metabolism in a wide variety of biological settings including but not limited to: immunology, cancer and (cancer) stem cells. Show less
Activity-based proteomics of the endocannabinoid system
Rooden, E.J. van 2018
Activity-based proteomics of the endocannabinoid system
Doctoral Thesis
open access
2019-07-13T00:00:00Z; 2019-02-01T00:00:00Z; 2019-06-14T00:00:00Z; 2019-07-13T00:00:00Z
This thesis describes the use of an activity-based proteomics method to study the endocannabinoid system. A protocol for label-free chemical proteomics to measure serine hydrolase activity in mouse... Show moreThis thesis describes the use of an activity-based proteomics method to study the endocannabinoid system. A protocol for label-free chemical proteomics to measure serine hydrolase activity in mouse tissue is described. This method is used to compare a Niemann-Pick Type C mouse model to healthy mice. Additionally, several novel activity-based probes for the enzymes diacylglycerol lipase alpha and a/b-hydrolase domain containing protein 6 are described. Show less
Activity-based protein profiling of diacylglycerol lipases
Baggelaar, M.P. 2017
Activity-based protein profiling of diacylglycerol lipases
Doctoral Thesis
open access
2018-09-06T00:00:00Z; 2018-09-06T00:00:00Z; 2018-09-06T00:00:00Z; 2018-09-06T00:00:00Z
Diacylglycerol lipase (DAGL)-α and -β are enzymes responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol. Selective and reversible inhibitors are required to study the... Show moreDiacylglycerol lipase (DAGL)-α and -β are enzymes responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol. Selective and reversible inhibitors are required to study the function of DAGLs in neuronal cells in an acute and temporal fashion. The work described in this thesis has led to the identification of an activity-based probe (ABP) for DAGL-α. This ABP was instrumental for the identification of a new class of highly selective DAGL inhibitors. These novel inhibitors can be used to investigate the role of the diacylglycerol lipases in metabolic syndrome and neurodegenerative diseases such a Parkinson’s disease, Alzheimer’s disease and Multiple Sclerosis. Show less
Synthetic tools to illuminate matrix metalloproteinase and proteasome activities
Geurink, P.P. 2010
Synthetic tools to illuminate matrix metalloproteinase and proteasome activities
Doctoral Thesis
open access
2012-10-06T00:00:00Z; 2012-10-06T00:00:00Z; 2012-10-06T00:00:00Z; 2012-10-06T00:00:00Z; 2012-10-06T00:00:00Z; 2012-10-06T00:00:00Z; 2012-10-06T00:00:00Z; 2012-10-06T00:00:00Z; 2012-10-06T00:00:00Z
This thesis describes the design, synthesis and application of chemical tools for the activity-based protein profiling of proteases, with the main focus on matrix metalloproteinases (MMPs) and the... Show moreThis thesis describes the design, synthesis and application of chemical tools for the activity-based protein profiling of proteases, with the main focus on matrix metalloproteinases (MMPs) and the proteasome. The use of photoaffinity labeling is described and the thesis starts with an extensive outline of the three most often used photoreactive groups and their application in (recently published) protein profiling studies. Targeting MMPs is performed by application of photoaffinity probes, while the proteasome is commonly targeted by so-called suicide inhibitors. The last experimental chapter deals with the creation of a novel chemoselective cleavable linker and its use in the pull-down of active proteasome subunits. Show less