Publications by authors named "Simon Nadal"
Objectives: Multiple myeloma (MM) is a plasma cell malignancy characterized by a monoclonal expansion of plasma cells that secrete a characteristic M-protein. This M-protein is crucial for diagnosis and monitoring of MM in the blood of patients. Recent evidence has emerged suggesting that N-glycosylation of the M-protein variable (Fab) region contributes to M-protein pathogenicity, and that it is a risk factor for disease progression of plasma cell disorders.
View Article and Find Full Text PDFDrugs that target histone deacetylase (HDAC) entered the pharmacopoeia in the 2000s. However, some enigmatic phenotypes suggest off-target engagement. Here, we developed a quantitative chemical proteomics assay using immobilized HDAC inhibitors and mass spectrometry that we deployed to establish the target landscape of 53 drugs.
View Article and Find Full Text PDFPost-translational modifications (PTMs) greatly expand the structures and functions of proteins in nature. Although synthetic protein functionalization strategies allow mimicry of PTMs, as well as formation of unnatural protein variants with diverse potential functions, including drug carrying, tracking, imaging and partner crosslinking, the range of functional groups that can be introduced remains limited. Here we describe the visible-light-driven installation of side chains at dehydroalanine residues in proteins through the formation of carbon-centred radicals that allow C-C bond formation in water.
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- Fragment-based drug discovery (FBDD) helps researchers explore a large variety of potential drug compounds by Screening small fragments and determining how they interact with proteins using techniques like X-ray crystallography.
- In a study, researchers screened 15 very small fragments computationally and found three key interaction sites on the FKBP51 FK1 domain, achieving a hit rate of 40% with six successful X-ray co-structures.
- The study suggests a hybrid approach that combines computational methods, X-ray screening, and N HSQC NMR to quickly identify promising drug candidates and their binding interactions.
Chromatin is the physiological template of genetic information in all eukaryotic cells, a highly organised complex of DNA and histone proteins central in regulating gene expression and genome organisation. A multitude of histone post-translational modifications (PTMs) have been discovered, providing a glance into the complex interplay of these epigenetic marks in cellular processes. In the last decade, synthetic and chemical biology techniques have emerged to study these modifications, including genetic code expansion, histone semisynthesis and post-translational chemical mutagenesis.
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