A5046853170- Computational Drug Discovery Methods
- Pharmacogenetics and Drug Metabolism
- Analytical Chemistry and Chromatography
- Drug Transport and Resistance Mechanisms
- Estrogen and related hormone effects
- Chemical Synthesis and Analysis
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Amino Acid Enzymes and Metabolism
- Ion channel regulation and function
- Molecular spectroscopy and chirality
- Advanced Chemical Physics Studies
- Organic Chemistry Cycloaddition Reactions
- Bacterial Genetics and Biotechnology
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Structure and Function
- Crystallography and molecular interactions
- Hormonal Regulation and Hypertension
- Protein Kinase Regulation and GTPase Signaling
- Protein Structure and Dynamics
- Synthesis and Properties of Aromatic Compounds
- RNA and protein synthesis mechanisms
- Molecular Spectroscopy and Structure
- Hormonal and reproductive studies
- Photochemistry and Electron Transfer Studies
University of Copenhagen
2016-2025
Bioneer (Denmark)
2011-2014
Nord University
2014
Technical University of Denmark
2006-2011
University of Southern Denmark
2004-2010
University of New Mexico
2008
Rigshospitalet
2005
University of Ghana
2004
Philipps University of Marburg
2003
National Cancer Institute
2003
Endocrine-disrupting chemicals (EDCs) may impact the development of prostate cancer (PCa) by altering steroid metabolism. Although their exact mechanism action in controlling tumor growth is not known, EDCs inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 which are involved production androgens estrogens. High levels circulating linked to PCa men and Polycystic Ovary Syndrome (PCOS) women. Essential oils metabolites, like lavender oil tea tree oil, have been reported act potential...
Abstract Cytochrome P450s of the CYP79 family catalyze two N‐hydroxylation reactions, converting a selected number amino acids into corresponding oximes. The sorghum genome ( Sorghum bicolor ) harbours nine CYP79A encoding genes, and here sequence comparisons CYP79As along with their substrate recognition sites (SRSs) are provided. specificity previously uncharacterized was investigated by transient expression in Nicotiana benthamiana subsequent transformation oximes formed stable oxime...
Prostate cancer (PCa) is one of the most prevalent malignancies affecting men worldwide, and androgen deprivation therapy (ADT) a primary treatment approach. CYP17A1 inhibitors like abiraterone target steroidogenic pathway to reduce levels, but their clinical efficacy limited by drug resistance adverse effects. This study reports synthesis evaluation novel derived from previously identified hit compound. Several analogs were synthesised, including an unexpected di-cyano derivative, which...
The serotonin transporter (SERT) regulates extracellular levels of the neurotransmitter (5-hydroxytryptamine) in brain by facilitating uptake released 5-hydroxytryptamine into neuronal cells. SERT is target for widely used antidepressant drugs, including imipramine, fluoxetine, and (S)-citalopram, which are competitive inhibitors transport function. Knowledge molecular details binding sites has been limited due to lack structural data on SERT. Here, we present a characterization...
The cytochrome P450 (P450) superfamily plays an important role in the metabolism of drug compounds, and it is therefore highly desirable to have models that can predict whether a compound interacts with specific isoform P450s. In this work, we provide silico for classification CYP1A2 inhibitors noninhibitors. Training test sets consisted approximately 400 7000 respectively. Various machine learning techniques, such as binary quantitative structure activity relationship, support vector (SVM),...
Cytochromes P450 are the most important class of drug metabolizing enzymes. Prediction metabolism is in development new drugs, to understand and reduce adverse reactions animal testing.SMARTCyp 3.0 an updated version our previous web server for prediction site-of-metabolism Cytochrome P450-mediated metabolism, now Python 3 with increased structural coverage features. The SMARTCyp program a first principle-based method using density functional theory determined activation energies more than...
Metabolic control is mediated by the dynamic assemblies and function of multiple redox enzymes. A key element in these assemblies, P450 oxidoreductase (POR), donates electrons selectively activates numerous (>50 humans >300 plants) cytochromes (CYPs) controlling metabolism drugs, steroids xenobiotics natural product biosynthesis plants. The mechanisms underlying POR-mediated CYP remain poorly understood to date no ligand binding has been described regulate specificity POR. Here, using a...
ABSTRACT Three β-galactosidase genes from Bifidobacterium bifidum DSM20215 and one gene infantis DSM20088 were isolated characterized. The three B. β-galactosidases exhibited a low degree of amino acid sequence similarity to each other previously published classified as family 2 glycosyl hydrolases. Likewise, the was distantly related enzymes 42 One , termed BIF3, is most probably an extracellular enzyme, since it contained signal which cleaved off during heterologous expression enzyme in...
The human Ether-a-go-go Related Gene (hERG) potassium channel is one of the major critical factors associated with QT interval prolongation and development arrhythmia called Torsades de Pointes (TdP). It has become a growing concern both regulatory agencies pharmaceutical industries who invest substantial effort in assessment cardiac toxicity drugs. silico tools to filter out potential hERG inhibitors early stages drug discovery process considerable interest. Here, we describe binary...
In the present work, Henderson−Hasselbalch (HH) equation has been employed for development of a tool prediction pH-dependent aqueous solubility drugs and drug candidates. A new method intrinsic was developed, based on artificial neural networks that have trained druglike PHYSPROP subset 4548 compounds. For acid/base dissociation coefficients, commercial Marvin used, following validation data set 467 molecules from database. The best performing network predictions cross-validated root mean...
With the availability of an increasing number high resolution 3D structures human cytochrome P450 enzymes, structure-based modeling tools are more readily used. In this study we explore possibilities using docking and scoring experiments on 1A2. Three different questions have been addressed: 1. Binding orientations conformations were successfully predicted for various substrates. 2. A virtual screen was performed with satisfying enrichment rates. 3. classification individual compounds into...
A formulation in terms of projection operators the Van Vleck trans-formation is presented. Explicit formulae through eighth order are given, and eleventh may be reached fairly simply. Such high orders relevant for Born-Oppenheimer separation. It proved that transformation conserves symmetry. special given product spaces. The Foldy-Wouthuysen treated as an example.
A micro‐modification of the MLC technique is described, using 5 × 10 4 responding cells per single culture in round bottomed microtiter plates. Over a wide range, there linear relation between number grown well and obtained response; with chosen, linearity log dose stimulating response scale. The system normally allows phase growth (or near to this) for 120 h. has primarily been designed large scale population genetic investigations X‐rayed stimulator stored frozen irradiated state. It suits...
Abstract Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to endogenous substrates. Abiraterone structurally substrates other cytochrome enzymes involved steroidogenesis, and interference can pose liability terms side effects. Using non-steroidal scaffolds expected enable design compounds...
With a view to the rational design of selective GSK-3β inhibitors, 3D-QSAR CoMSIA models were developed for inhibition three serine/threonine kinases CDK1/cyclin B, CDK5/p25, and by compounds from paullone inhibitor family. The are based on kinase data 52 entities, which aligned docking routine into ATP-binding cleft B homology model. Variation grid spacing column filtering used during optimization models. predictive ability was shown leave-one-out cross-validation prediction an independent...
In this work, eight different scoring functions have been combined with the aim of improving prediction protein−ligand binding conformations and affinities. The obtained scores were analyzed using multivariate statistical methods to generate expressions, ability (1) select best candidate between docked an inhibitor (MultiSelect) (2) quantify affinity (MultiScore). By use docking program GOLD, 40 inhibitors into active site three matrix metalloproteinases (MMP's), yielding a total 120...
A homology model of the human GABA transporter (GAT-1) based on recently reported crystal structures bacterial leucine from Aquifex aeolicus (LeuT) was developed. The stability resulting embedded in a membrane environment analyzed by extensive molecular dynamics (MD) simulations. Based docking studies and subsequent MD simulations three compounds, endogenous ligand two potent inhibitors, (R)-nipecotic acid anti-epilepsy drug tiagabine, various binding modes were identified are discussed....
Aldehyde oxidase (AO) is a molybdenum-containing enzyme involved in the clearance of drug compounds containing aldehydes and N-containing heterocyclic fragments. AO has gained considerable interest recent years because examples too fast development. Thus, it important to be able predict AO-mediated metabolism. Therefore, we have characterized structural energetic aspects different mechanisms with density functional theory using molybdenum cofactor as model for reactive part enzyme. For...