A5085467055- Cellular transport and secretion
- Biochemical and Structural Characterization
- Lipid Membrane Structure and Behavior
- Calcium signaling and nucleotide metabolism
- Retinal Development and Disorders
- Axon Guidance and Neuronal Signaling
- Hippo pathway signaling and YAP/TAZ
- Mass Spectrometry Techniques and Applications
- Cell Adhesion Molecules Research
- Electrochemical sensors and biosensors
- Research on Leishmaniasis Studies
- Ion Channels and Receptors
- Receptor Mechanisms and Signaling
- Endoplasmic Reticulum Stress and Disease
- Photoreceptor and optogenetics research
- Lysosomal Storage Disorders Research
- Complement system in diseases
- Trypanosoma species research and implications
- Adenosine and Purinergic Signaling
- Metabolomics and Mass Spectrometry Studies
- Advanced biosensing and bioanalysis techniques
- Autophagy in Disease and Therapy
- Cardiac electrophysiology and arrhythmias
- Biochemical and Molecular Research
- Sleep and Wakefulness Research
Freie Universität Berlin
2011-2019
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2012-2016
SocraTec R&D (Germany)
2013
Dynamin GTPase activity increases when it oligomerizes either into helices in the presence of lipid templates or rings SH3 domain proteins. Dynasore is a dynamin inhibitor moderate potency ( IC 50 ˜ 15 μM vitro ). We show that dynasore binds stoichiometrically to detergents used for drug screening, drastically reducing its = 479 μM) and research tool utility. synthesized focused set dihydroxyl trihydroxyl analogs called Dyngo™ compounds, five which had improved potency, reduced detergent...
Chlorpromazine is a phenothiazine‐derived antipsychotic drug ( APD ) that inhibits clathrin‐mediated endocytosis CME in cells by an unknown mechanism. We examined whether its action and of other APDs might be mediated the GTPase activity dynamin. Eight eight inhibited dynamin I dynI 2–12 µ m range, most potent being trifluoperazine IC 50 2.6 ± 0.7 ). They also II dynII at similar concentrations. Typical atypical not based on phenothiazine scaffold were 8‐ to 10‐fold less (haloperidol...
Six focused rhodanine-based libraries, 60 compounds in total, were synthesized and evaluated as potential dynamin I GTPase inhibitors. Twenty-six more potent than the lead compound with 13 returning IC50 values ≤10 μM, making Rhodadyn series among most active inhibitors reported. Two analogues highly effective at blocking receptor-mediated endocytosis: C10 D10 IC50(RME) = 7.0 ± 2.2 5.9 1.0 respectively. These are equipotent best reported in-cell
We reported the first small molecule inhibitors of interaction between clathrin N-terminal domain (TD) and endocyctic accessory proteins (i.e., inhibition1). Initial screening a ∼17 000 ChemBioNet library identified 1. Screening an existing in-house propriety four substituted 1,8-napthalimides as ∼80–120 μM inhibitors. Focused development gave 3-sulfo-N-(4-aminobenzyl)-1,8-naphthalimide, potassium salt (18, IC50 ≈ 18 μM). A second targeting 4-aminobenzyl moiety was developed, analogues...
The volume-regulated anion channel (VRAC) plays an important role in osmotic cell volume regulation. In addition, it is involved various physiological processes such as insulin secretion, glia-neuron communication and purinergic signaling. VRAC formed by hetero-hexamers of members the LRRC8 protein family, which consists five members, LRRC8A-E. LRRC8A essential subunit for functionality VRAC. Its obligate heteromerization with at least one its paralogues, LRRC8B-E, determines biophysical...
The DNA-programmed peptide display in brain extract revealed a co-operation between the binding sites on AP-2 alpha-appendage domain.
Structurally related inhibitors of a shared therapeutic target may differ regarding potential toxicity issues that are caused by different off-target bindings. We devised differential competition capture compound mass spectrometry (dCCMS) strategy to effectively differentiate profiles. Tolcapone and entacapone potent catechol-O-methyl transferase (COMT) for the treatment Parkinson's disease. is also known its hepatotoxic side effects even though it therapeutically more than entacapone. Here,...
The development of a (Z)-5-((6,8-dichloro-4-oxo-4H-chromen-3-yl)methylene)-2-thioxothiazolidin-4-one (2), rhodanine-based lead that led to the Pitstop® 2 family clathrin inhibitors is described herein. Head group substitution and bioisosteric replacement rhodanine core with 2-aminothiazol-4(5H)-one scaffold eliminated off target dynamin activity. A series N-substituents gave first phenylglycine (20, IC50 ∼ 20 μM) then phenyl (25, 7.1 1-napthyl sulfonamide (26, compound, 1.9 analogues good...
Abstract During sleep, the time-compressed replay of engrams acquired during preceding wakefulness drives memory consolidation. We demonstrate in healthy humans that direct electrical coupling between neurons via gap junctions, i.e., synapses, contributes to this beneficial effect sleep. Twenty male participants learned a declarative word-pair task and procedural finger sequence tapping before receiving antimalarial mefloquine is known block synapses. Retrieval was tested after retention...