A5074147846- Chemical Synthesis and Analysis
- Signaling Pathways in Disease
- Ferrocene Chemistry and Applications
- Enzyme Catalysis and Immobilization
- Heat shock proteins research
- Biofuel production and bioconversion
- Aldose Reductase and Taurine
- Catalytic C–H Functionalization Methods
- Computational Drug Discovery Methods
- Microbial Natural Products and Biosynthesis
- Click Chemistry and Applications
- Microbial Metabolic Engineering and Bioproduction
- Protein Degradation and Inhibitors
- Protein Structure and Dynamics
- Legume Nitrogen Fixing Symbiosis
- Ion Channels and Receptors
- DNA and Nucleic Acid Chemistry
- Synthesis and Catalytic Reactions
- Carbohydrate Chemistry and Synthesis
- Enzyme Structure and Function
Technical University of Darmstadt
2023-2025
Max Planck Institute for Medical Research
2023
University of Bristol
2022
Macrocycles are abundantly used by nature to enable cell-permeable bioactive molecules. Synthetic non-peptidic macrocycles also increasingly considered as modalities for difficult-to-bind proteins but guidelines macrocyclization only beginning emerge. thought constrain the available conformations allow residual flexibility, latter being poorly understood. Here we show that even medium-sized display an unexpected high conformational plasticity, when bound their protein target. Minor...
In recent years, the selective inhibition of FKBP51 has emerged as a possible treatment for chronic pain, obesity-induced diabetes, or depression. All currently known advanced FKBP51-selective inhibitors, including widely used SAFit2, contain cyclohexyl residue key motif enabling selectivity over closest homologue and anti-target FKBP52. During structure-based SAR exploration, we surprisingly discovered thiophenes highly efficient replacement moieties that retain strong SAFit-type inhibitors...
Macrocycles are abundantly used by nature to enable cell‐permeable bioactive molecules. Synthetic non‐peptidic macrocycles also increasingly considered as modalities for difficult‐to‐bind proteins but guidelines macrocyclization only beginning emerge. thought constrain the available conformations allow residual flexibility, latter being poorly understood. Here we show that even medium‐sized display an unexpected high conformational plasticity, when bound their protein target. Minor...
In recent years, rationally designed macrocycles have emerged as promising therapeutic modalities for challenging drug targets. Macrocycles can improve affinity, selectivity, and pharmacokinetic (PK) parameters, possibly via providing semirigid, preorganized scaffolds. Nevertheless, how macrocyclization affects PK-relevant properties is still poorly understood. To address this question, we systematically generated compared 15 matched molecular pairs of structurally similar linear analogs. We...
The genomes of anaerobic ammonium-oxidizing (anammox) bacteria contain a gene cluster comprising genes unusual fatty acid biosynthesis enzymes that were suggested to be involved in the synthesis unique "ladderane" lipids produced by these organisms. This encodes an acyl carrier protein (denoted as "amxACP") and variant FabZ, ACP-3-hydroxyacyl dehydratase. In this study, we characterize enzyme, which call anammox-specific FabZ ("amxFabZ"), investigate unresolved biosynthetic pathway ladderane...
A new practical, catalytic, and highly stereoselective method for directly accessing 1,1-α,α′-linked 2-deoxy trehalose analogues via AuCl3-catalyzed dehydrative glycosylation using hemiacetal glycosyl donors acceptors is described. The relies on the chemoselective Brønsted acid-type activation of tribenzylated hemiacetals in presence other less reactive hemiacetals.
In recent years the selective inhibition of FKBP51 has emerged as a possible treatment for chronic pain, obesity-induced diabetes, or depression. All currently known advanced FKBP51-selective inhibitors, including widely used SAFit2, contain cyclohexyl residue key motif enabling selectivity over closest homolog and anti-target FKBP52. During structure-based SAR exploration we surprisingly discovered thiophenes highly efficient replacement moieties that retain strong SAFit-type inhibitors...