ChemBioChem

Journal: ChemBioChem

Abbreviation

ChemBioChem

Publisher

Wiley-VCH

ISSN

1439-4227
1439-7633

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Publications1 - 10 of 37

A molecular dynamics study of the ASC and NALP1 pyrin domains at neutral and low pH
Gattin, Zrinka; van Gunsteren, Wilfred F. (2008)
ChemBioChem
Quantum Computing for Molecular Biology
Baiardi, Alberto; Christandl, Matthias; Reiher, Markus (2023)
ChemBioChem
Molecular biology and biochemistry interpret microscopic processes in the living world in terms of molecular structures and their interactions, which are quantum mechanical by their very nature. Whereas the theoretical foundations of these interactions are well established, the computational solution of the relevant quantum mechanical equations is very hard. However, much of molecular function in biology can be understood in terms of classical mechanics, where the interactions of electrons and nuclei have been mapped onto effective classical surrogate potentials that model the interaction of atoms or even larger entities. The simple mathematical structure of these potentials offers huge computational advantages; however, this comes at the cost that all quantum correlations and the rigorous many-particle nature of the interactions are omitted. In this work, we discuss how quantum computation may advance the practical usefulness of the quantum foundations of molecular biology by offering computational advantages for simulations of biomolecules. We not only discuss typical quantum mechanical problems of the electronic structure of biomolecules in this context, but also consider the dominating classical problems (such as protein folding and drug design) as well as data-driven approaches of bioinformatics and the degree to which they might become amenable to quantum simulation and quantum computation.
Comparison of the NMR spectroscopy solution structures of pyranosyl-RNA and its nucleo-delta-peptide analogue
Ilin, Sergey; Schlönvogt, Irene; Ebert, Marc-Olivier; et al. (2002)
ChemBioChem
Proton‐Detected Solid‐State NMR of the Cell‐Free Synthesized α‐Helical Transmembrane Protein NS4B from Hepatitis C Virus
Jirasko, Vlastimil; Lakomek, Nils-Alexander; Penzel, Susanne; et al. (2020)
ChemBioChem
Proton‐detected 100 kHz magic‐angle‐spinning (MAS) solid‐state NMR is an emerging analysis method for proteins with only hundreds of microgram quantities, and thus allows structural investigation of eukaryotic membrane proteins. This is the case for the cell‐free synthesized hepatitis C virus (HCV) nonstructural membrane protein 4B (NS4B). We demonstrate NS4B sample optimization using fast reconstitution schemes that enable lipid‐environment screening directly by NMR. 2D spectra and relaxation properties guide the choice of the best sample preparation to record 2D ¹H‐detected ¹H,¹⁵N and 3D ¹H,¹³C,¹⁵N correlation experiments with linewidths and sensitivity suitable to initiate sequential assignments. Amino‐acid‐selectively labeled NS4B can be readily obtained using cell‐free synthesis, opening the door to combinatorial labeling approaches which should enable structural studies.
Preclinical Evaluation of the Reversible Monoacylglycerol Lipase PET Tracer (R)-[11C]YH132: Application in Drug Development and Neurodegenerative Diseases
He, Yingfang; Delparente, Aro; Jie, Caitlin V.M.L.; et al. (2024)
ChemBioChem
Monoacylglycerol lipase (MAGL) plays a crucial role in the degradation of 2-arachidonoylglycerol (2-AG), one of the major endocannabinoids in the brain. Inhibiting MAGL could lead to increased levels of 2-AG, which showed beneficial effects on pain management, anxiety, inflammation, and neuroprotection. In the current study, we report the characterization of an enantiomerically pure (R)-[¹¹C]YH132 as a novel MAGL PET tracer. It demonstrates an improved pharmacokinetic profile compared to its racemate. High in vitro MAGL specificity of (R)-[¹¹C]YH132 was confirmed by autoradiography studies using mouse and rat brain sections. In vivo, (R)-[¹¹C]YH132 displayed a high brain penetration, and high specificity and selectivity toward MAGL by dynamic PET imaging using MAGL knockout and wild-type mice. Pretreatment with a MAGL drug candidate revealed a dose-dependent reduction of (R)-[¹¹C]YH132 accumulation in WT mouse brains. This result validates its utility as a PET probe to assist drug development. Moreover, its potential application in neurodegenerative diseases was explored by in vitro autoradiography using brain sections from animal models of Alzheimer's disease and Parkinson's disease.
Targeting Cellular Lipid Rafts for Dynamic Nuclear Polarization Nuclear Magnetic Resonance
Overall, Sarah A.; Eck, Agnes; Wilson, Ancy T.; et al. (2026)
ChemBioChem
Lipid rafts serve as important platforms for membrane and signaling proteins. The mechanisms underlying the targeting of nonmyristylated drugs and proteins to lipid rafts remain poorly understood, and the specific structural interactions that govern their localization and stabilization within these membrane microdomains are unclear. This is largely due to a lack of techniques with angstrom resolution that are capable of investigating these membrane microdomains. In-cell nuclear magnetic resonance (NMR) spectroscopy is the only technique with the potential for obtaining such information. Here, we introduce an approach to investigate lipid rafts by in-cell dynamic nuclear polarization (DNP) NMR by covalently linking the polarizing agent AsymPol to the raft-specific protein Ostreolysin A (OlyA). We demonstrate the method's specificity via fluorescence microscopy and obtain DNP enhancements even at very low concentrations of spin-labeled OlyA, whose heterogeneous localization can be identified in DNP buildup curves. Through this work, we identify cross-effect efficiency as a key limiting factor in the pursuit of lipid raft-targeted DNP, revealing important areas of development for enabling targeted DNP of these important cellular structures.
Twenty-five Years of DNA-Encoded Chemical Libraries
Neri, Dario (2017)
ChemBioChem
Exploring the structural space of the galectin-1-ligand interaction.
Bertleff-Zieschang, Nadja; Bechold, Julian; Grimm, Clemens; et al. (2017)
ChemBioChem
Synthesis and Preliminary Evaluation of Tanshinone Mimic Conjugates for Mechanism of Action Studies
Assoni, Giulia; Assunção Carreira, Ágata Sofia; Tomiello, Matteo; et al. (2025)
ChemBioChem
Human antigen R (HuR) is an RNA binding protein (RBP) belonging to the ELAV (Embryonic Lethal Abnormal Vision) family, which stabilizes mRNAs and regulates the expression of multiple genes. Its altered expression or localization is related to pathological features such as cancer or inflammation. Dihydrotanshinone I (DHTS I) is a naturally occurring, tetracyclic ortho-quinone inhibitor of the HuR-mRNA interaction. Our earlier efforts led to the identification of a synthetic Tanshinone Mimic (TM) 2 with improved affinity for HuR. Here we report five new TM probes 3-5 bearing a detection-promoting moiety (either photo affinity probe - PAP or biotin) as a para-substituent on the phenyl-sulphonamide for mechanism of action (MoA) studies. Biological and biochemical assays were used to characterize the novel TM conjugates 3-5. They showed similar toxic activity in HuR-expressing triple-negative breast cancer MDA-MB-231 cells, with micromolar CC₅₀s. REMSAs revealed that photoactivatable groups (4 a and 4 b), but not biotin (5 a and 5 b), prevented conjugates' ability to disrupt rHuR-RNA complexes. Further biochemical studies confirmed that biotinylated probes, in particular 5 a, can be used to isolate rM1 M2 from solutions, taking advantage of streptavidin-coated magnetic beads, thus being the most promising HuR inhibitor to be used for further MoA studies in cell lysates.
Design of an S-Allylcysteine in situ production and incorporation system based on a novel pyrrolysyl-tRNA synthetase variant
Exner, Matthias P.E.; Kuenzl, Tilmann; To, Tuyet Mai T.; et al. (2017)
ChemBioChem

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