A5016910204- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- X-ray Diffraction in Crystallography
- Click Chemistry and Applications
- Receptor Mechanisms and Signaling
- DNA and Nucleic Acid Chemistry
- Neuropeptides and Animal Physiology
- Advanced biosensing and bioanalysis techniques
- Cyclopropane Reaction Mechanisms
- Asymmetric Synthesis and Catalysis
- Forensic Toxicology and Drug Analysis
- RNA Interference and Gene Delivery
- Computational Drug Discovery Methods
- Asymmetric Hydrogenation and Catalysis
- Synthesis and Catalytic Reactions
- Monoclonal and Polyclonal Antibodies Research
- Synthetic Organic Chemistry Methods
- Analytical Chemistry and Chromatography
- Organophosphorus compounds synthesis
- Metabolomics and Mass Spectrometry Studies
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- Plant biochemistry and biosynthesis
- Alcohol Consumption and Health Effects
- HIV/AIDS drug development and treatment
University of Copenhagen
2011-2024
Novo Nordisk (Denmark)
2020-2024
Atrium Health Wake Forest Baptist
2018
Institute of Human Genetics
2012-2014
Columbia College - Missouri
2012-2014
Amsterdam University of Applied Sciences
2012-2014
The University of Adelaide
2007-2013
Vrije Universiteit Brussel
2011
The University of Texas at San Antonio
2008-2009
University of Warwick
2009
Abstract The ability to synthesise small peptidomimetics that mimic the secondary structure of proteins is an ever expanding area research directed at sourcing new medicinal agents and biological probes. A significant current challenge protein epitopes under physiological conditions using are easy prepare. copper‐ ruthenium‐catalysed Huisgen cycloaddition reactions provide such a general synthetic method, with resulting 1,2,3‐triazoles being good peptide bond mimics. prepare both 1,4‐...
Small molecule therapeutics represent the majority of FDA-approved drugs. Yet, many attractive targets are poorly tractable by small molecules, generating a need for new therapeutic modalities. Due to their biocompatibility profile and structural versatility, peptide-based possible solution. Additionally, in past two decades, advances peptide design, delivery, formulation, devices have occurred, making peptides an modality. However, manufacturing is often limited solid-phase synthesis...
Chromatographic purification is an integrated part of organic synthesis. The Dry Column Vacuum Chromatography presented here, has excellent resolving power, easily applied to large scale chromatography (up 100 g) and fast. Furthermore, the technique economical environmentally friendly due significant reductions in solvent amount silica used. Therefore, it alternative commonly used Flash for
Binding and signaling kinetics have previously proven important in validation of biased agonism at GPCRs. Here we provide a comprehensive kinetic pharmacological comparison clinically relevant μ-opioid receptor agonists, including the novel agonist oliceridine (TRV130) which is clinical trial for pain management. We demonstrate that bias profile observed selected agonists not time-dependent with dramatic differences their binding properties can display same degree bias. analyses...
Binary solvent mixtures with a suitable polarity and viscosity profile are viable green alternatives to DMF in solid-phase peptide synthesis.
The composition of green binary solvent mixtures is used as a tool to mitigate side-reactions in SPPS.
Solid-phase peptide synthesis (SPPS) is an efficient platform technology for synthesizing synthetic peptides but has environmental downside due to the use of vast amounts toxic solvents. In recent years, a big effort been made replace these solvents with more environmentally benign alternatives; however, this work not had significant effect on reducing PMI and carbon footprint SPPS. Herein, we demonstrate that by adding low concentration Oxyma Pure waste stream after Fmoc-removal, simple...
There is a well documented need to replenish the antibiotic pipeline with new agents combat rise of drug resistant bacteria. One strategy resistance discover chemical classes immune current mechanisms that inhibit essential metabolic enzymes. Many obvious targets have no homologous isozyme in human host now been investigated. Bacterial closely related homologue represent frontier discovery. However, avoid potential toxicity host, these inhibitors must very high selectivity for bacterial...
Privileged structures have been used in drug discovery targeting G protein-coupled receptors (GPCR) and other protein classes for more than 20 years. Their rich activity profiles drug-like characteristics lend themselves to increased productivity hit identification lead optimisation. Recently we discovered two allosteric modulators 1 2 the receptor GPRC6A incorporating privileged 2-phenyl-indole scaffold, functionalised at 3-position. In order develop new potential ligands engaged...
Among the new psychoactive substances (NPS) that have recently emerged on market, many of synthetic opioids shown to be particularly harmful. A analogue fentanyl, N ‐phenyl‐ ‐[1‐(2‐phenethyl)piperidin‐4‐yl]prop‐2‐enamide (acrylfentanyl), was identified in powder from a seized capsule found at forensic psychiatric ward Denmark. Gas chromatography with mass spectrometry (GC‐MS) precursor fentanyls, ‐phenyl‐1‐(2‐phenylethyl)piperidin‐4‐amine; however, 1‐(2‐phenethyl)piperidin‐4‐one, not...
Abstract With the emergence of copper‐catalysed Huisgen cycloaddition use azide‐ and alkyne‐derivatised α‐amino acids has found widespread within most chemistry disciplines. Despite a growing interest in these building blocks researchers are struggling to identify best way for their synthesis. In this review we have compiled available methods synthesising optically active that can be prepared from readily acids. We highlight number commonly overlooked problems associated with existing direct...
GPR139 is an orphan G protein-coupled receptor that expressed primarily in the brain. Not much known regarding function of GPR139. Recently we have shown activated by amino acids l-tryptophan and l-phenylalanine (EC50 values 220 μM 320 μM, respectively), as well di-peptides comprised aromatic acids. This led us to hypothesize may be peptides. Sequence alignment binding cavities all class A GPCRs, revealed pocket melanocortin 4 similar Based on chemogenomics principle "similar targets bind...
Green binary solvent mixtures with a polarity and viscosity close to that of DMF perform similarly in solid-phase peptide synthesis (SPPS). However, while coupling reactions readily proceed solvents significantly lower than DMF, high is essential for Fmoc-removal using piperidine, which limits the options green SPPS solvents. Herein, we report our efforts expand available space SPPS. We identified pyrrolidine as an efficient base enable less polar also favor reactions, such dimethyl...
Gamma-hydroxybutyric acid (GHB) is an important analyte in clinical and forensic toxicology with a narrow detection window of 3–6 h. In the search improved methods, existence vivo glucuronated GHB metabolite (GHB-GLUC) was hypothesized. Chemically pure standards GHB-GLUC deuterated analogue for chromatography were synthesized. Liquid tandem mass spectrometry used targeted analysis anonymous urine samples (n = 50). found concentrations ranging from 0.11 to 5.0 µg/mL (mean: 1.3 ± 1.2 µg/mL)....
Two synthetic routes for the synthesis of amino-triazolodiazepine (Ata) scaffolds are presented. The scope both these proceeding through key intra- and intermolecular Huisgen cycloaddition reactions is discussed. replacement His-Pro dipeptide segment in angiotensin IV by mimetic Ata-Gly subsequent biological evaluation two inhibitory enzyme assays validated use Ata moiety as a His mimic given equipotency peptidic analogs.