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View article: Design, Synthesis, and Molecular Evaluation of S<sub>N</sub>Ar‐Reactive <i>N</i>‐(6‐Fluoro‐3‐Nitropyridin‐2‐yl)Isoquinolin‐3‐Amines as Covalent USP7 Inhibitors Reveals an Unconventional Binding Mode
Design, Synthesis, and Molecular Evaluation of S<sub>N</sub>Ar‐Reactive <i>N</i>‐(6‐Fluoro‐3‐Nitropyridin‐2‐yl)Isoquinolin‐3‐Amines as Covalent USP7 Inhibitors Reveals an Unconventional Binding Mode Open
The cysteine protease ubiquitin‐specific protease 7 (USP7), also known as herpes‐associated ubiquitin‐specific protease (HAUSP), has gained increasing attention in recent years due to its proven overexpression in several cancer types and i…
View article: SNAr Reactive Pyrazine Derivatives as p53-Y220C Cleft Binders with Diverse Binding Modes
SNAr Reactive Pyrazine Derivatives as p53-Y220C Cleft Binders with Diverse Binding Modes Open
The promising pyrazine derivatives SN006/7-3, SN006/7-8, and SN006/7-9 were identified, occupying different subsites of the Y220C binding pocket. The compound SN006/7-8 substantially stabilized the thermosensitive cancer mutant Y220C by up…
View article: Extended receptor repertoire of an adenovirus associated with human obesity
Extended receptor repertoire of an adenovirus associated with human obesity Open
Human adenovirus type 36 (HAdV-D36) has been putatively linked to obesity in animals and has been associated with obesity in humans in some but not all studies. Despite extensive epidemiological research there is limited information about …
View article: Covalent Fragments Acting as Tyrosine Mimics for Mutant p53-Y220C Rescue by Nucleophilic Aromatic Substitution
Covalent Fragments Acting as Tyrosine Mimics for Mutant p53-Y220C Rescue by Nucleophilic Aromatic Substitution Open
The tumor suppressor p53 is frequently mutated in human cancers. The Y220C mutant is the ninth most common p53 cancer mutant and is classified as a structural mutant, as it leads to strong thermal destabilization and degradation by creatin…
View article: Cover Feature: Intramolecular Coupling and Nucleobase Transfer – How Cytochrome P450 Enzymes GymB<sub>x</sub> Establish Their Chemoselectivity (ChemCatChem 10/2024)
Cover Feature: Intramolecular Coupling and Nucleobase Transfer – How Cytochrome P450 Enzymes GymB<sub>x</sub> Establish Their Chemoselectivity (ChemCatChem 10/2024) Open
The Cover Feature shows an overview of the work presented in the Research Article by Shu-Ming Li, Georg Zocher, and co-workers. The authors report the structures of a new class of cyclodipeptide-modifying P450 enzymes named GymBx that are …
View article: Intramolecular Coupling and Nucleobase Transfer – How Cytochrome P450 Enzymes GymB<sub>x</sub> Establish Their Chemoselectivity
Intramolecular Coupling and Nucleobase Transfer – How Cytochrome P450 Enzymes GymB<sub>x</sub> Establish Their Chemoselectivity Open
Cyclodipeptides (CDPs) build an important class of secondary metabolites with a plethora of pharmacological impact such as antibiotic, cytotoxic, antifungal properties or even as anti‐Alzheimer drug candidates. The core structure of 2,5‐di…
View article: Viral capsid structural assembly governs the reovirus binding interface to NgR1
Viral capsid structural assembly governs the reovirus binding interface to NgR1 Open
We reveal how viral capsid protein organization and curvature critically influence the stability of reovirus–NgR1 interactions, with distinct differences observed between single proteins, 2D assemblies, and 3D viral particles.
View article: Invasive <i>Staphylococcus epidermidis</i> uses a unique processive wall teichoic acid glycosyltransferase to evade immune recognition
Invasive <i>Staphylococcus epidermidis</i> uses a unique processive wall teichoic acid glycosyltransferase to evade immune recognition Open
Staphylococcus epidermidis expresses glycerol phosphate wall teichoic acid (WTA), but some health care–associated methicillin-resistant S. epidermidis (HA-MRSE) clones produce a second, ribitol phosphate (RboP) WTA, resembling that of the …
View article: Principles and Applications of CF<sub>2</sub>X Moieties as Unconventional Halogen Bond Donors in Medicinal Chemistry, Chemical Biology, and Drug Discovery
Principles and Applications of CF<sub>2</sub>X Moieties as Unconventional Halogen Bond Donors in Medicinal Chemistry, Chemical Biology, and Drug Discovery Open
As an orthogonal principle to the established (hetero)aryl halides, we herein highlight the usefulness of CF2X (X = Cl, Br, or I) moieties. Using tool compounds bearing CF2X moieties, we study their chemical/metabolic stability and their l…
View article: Novel multifunctional glycan probes to elucidate specificities of diverse glycan recognition systems
Novel multifunctional glycan probes to elucidate specificities of diverse glycan recognition systems Open
Glycan microarrays of sequence-defined glycans are the most widely used approach for high-throughput studies of interactions of glycans with glycan binding proteins. Currently nitrocellulose (NC) coated or N-hydroxysuccinimide (NHS) functi…
View article: NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein
NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein Open
Nogo-66 receptor 1 (NgR1) binds a variety of structurally dissimilar ligands in the adult central nervous system to inhibit axon extension. Disruption of ligand binding to NgR1 and subsequent signaling can improve neuron outgrowth, making …
View article: A novel and highly specific Forssman antigen-binding protein from sheep polyomavirus
A novel and highly specific Forssman antigen-binding protein from sheep polyomavirus Open
Polyomaviruses are small, non-enveloped double-stranded DNA viruses of humans and other mammals, birds, and fish. Infections are usually asymptomatic and result in latency, however, some polyomaviruses can induce severe diseases, including…
View article: Structural and functional analysis of natural capsid variants suggests sialic acid-independent entry of BK polyomavirus
Structural and functional analysis of natural capsid variants suggests sialic acid-independent entry of BK polyomavirus Open
BK polyomavirus (BKPyV) is an opportunistic pathogen that uses the b-series gangliosides GD1b and GT1b as entry receptors. Here, we characterize the impact of naturally occurring VP1 mutations on ganglioside binding, VP1 protein structure,…
View article: Synthesis, Biochemical Characterization, and Genetic Encoding of a 1,2,4‐Triazole Amino Acid as an Acetyllysine Mimic for Bromodomains of the BET Family
Synthesis, Biochemical Characterization, and Genetic Encoding of a 1,2,4‐Triazole Amino Acid as an Acetyllysine Mimic for Bromodomains of the BET Family Open
Lysine acetylation is a charge‐neutralizing post‐translational modification of proteins bound by bromodomains (Brds). A 1,2,4‐triazole amino acid (ApmTri) was established as acetyllysine (Kac) mimic recruiting Brds of the BET family in con…
View article: Genetic diversity of Staphylococcus aureus wall teichoic acid glycosyltransferases affects immune recognition
Genetic diversity of Staphylococcus aureus wall teichoic acid glycosyltransferases affects immune recognition Open
Staphylococcus aureus is a leading cause of skin and soft tissue infections and systemic infections. Wall teichoic acids (WTAs) are cell wall-anchored glycopolymers that are important for S. aureus nasal colonization, phage-mediated horizo…
View article: Optimization of the precursor supply for an enhanced FK506 production in Streptomyces tsukubaensis
Optimization of the precursor supply for an enhanced FK506 production in Streptomyces tsukubaensis Open
Tacrolimus (FK506) is a macrolide widely used as immunosuppressant to prevent transplant rejection. Synthetic production of FK506 is not efficient and costly, whereas the biosynthesis of FK506 is complex and the level produced by the wild …
View article: Screening of a Halogen-Enriched Fragment Library Leads to Unconventional Binding Modes
Screening of a Halogen-Enriched Fragment Library Leads to Unconventional Binding Modes Open
We conceived the Halogen-Enriched Fragment Library (HEFLib) to investigate the potential of halogen bonds in the early stages of drug discovery. As the number of competitive interactions increases with ligand size, we reasoned that a bindi…
View article: Structural and functional analysis of natural capsid variants reveals sialic-acid independent entry of BK polyomavirus
Structural and functional analysis of natural capsid variants reveals sialic-acid independent entry of BK polyomavirus Open
BK Polyomavirus (BKPyV) is an opportunistic pathogen that causes nephropathy in kidney transplant recipients. The BKPyV major capsid protein, VP1, engages gangliosides, lipid-linked sialylated glycans at the cell surface, to gain entry int…
View article: Genetic diversity of <i>Staphylococcus aureus</i> wall teichoic acid glycosyltransferases affects immune recognition
Genetic diversity of <i>Staphylococcus aureus</i> wall teichoic acid glycosyltransferases affects immune recognition Open
Staphylococcus aureus ( S. aureus ) is a leading cause of skin and soft tissue infections and (hospital-acquired) systemic infections. Wall teichoic acids (WTAs) are cell wall-anchored glycopolymers that are important for S. aureus nasal c…
View article: Optimization of the precursor supply for an enhanced FK-506 production in <i>Streptomyces tsukubaensis</i>
Optimization of the precursor supply for an enhanced FK-506 production in <i>Streptomyces tsukubaensis</i> Open
Tacrolimus (FK-506) is a macrolide widely used as immunosuppressant to prevent transplant rejection. Synthetic production of FK-506 is not efficient and costly, whereas the biosynthesis of FK-506 is complex and the level produced by the wi…
View article: Revisiting a challenging p53 binding site: a diversity-optimized HEFLib reveals diverse binding modes in T-p53C-Y220C
Revisiting a challenging p53 binding site: a diversity-optimized HEFLib reveals diverse binding modes in T-p53C-Y220C Open
Fragment screening of the challenging drug target T-p53-Y220C with our diversity optimized HEFLib leads to diverse reversible and covalent binding modes.
View article: Exploring divalent conjugates of 5-<i>N</i>-acetyl-neuraminic acid as inhibitors of coxsackievirus A24 variant (CVA24v) transduction
Exploring divalent conjugates of 5-<i>N</i>-acetyl-neuraminic acid as inhibitors of coxsackievirus A24 variant (CVA24v) transduction Open
Coxsackievirus A24 variant (CVA24v) is responsible for several outbreaks and two pandemics of the highly contagious eye infection acute hemorrhagic conjunctivitis (AHC).
View article: <i>Ex Vivo</i> and <i>In Vivo</i> CD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26)
<i>Ex Vivo</i> and <i>In Vivo</i> CD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26) Open
The human species D Ad26 is being investigated as a low-seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor util…
View article: <i>Ex Vivo</i>and<i>In Vivo</i>CD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26)
<i>Ex Vivo</i>and<i>In Vivo</i>CD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26) Open
Human adenovirus serotype 26 (Ad26) is used as a gene-based vaccine against SARS-CoV-2 and HIV-1. Yet, its primary receptor portfolio remains controversial, potentially including sialic acid, CAR, integrins, and CD46. We and others have sh…
View article: Exploring the Effect of Structure-Based Scaffold Hopping on the Inhibition of Coxsackievirus A24v Transduction by Pentavalent N-Acetylneuraminic Acid Conjugates
Exploring the Effect of Structure-Based Scaffold Hopping on the Inhibition of Coxsackievirus A24v Transduction by Pentavalent N-Acetylneuraminic Acid Conjugates Open
Coxsackievirus A24 variant (CVA24v) is the primary causative agent of the highly contagious eye infection designated acute hemorrhagic conjunctivitis (AHC). It is solely responsible for two pandemics and several recurring outbreaks of the …
View article: The human neuronal receptor NgR1 bridges reovirus capsid proteins to initiate infection
The human neuronal receptor NgR1 bridges reovirus capsid proteins to initiate infection Open
Human Nogo-66 receptor 1 (NgR1) is a receptor for mammalian orthoreoviruses (reoviruses), but the mechanism of virus-receptor engagement is unknown. NgR1 binds a variety of structurally dissimilar ligands in the adult central nervous syste…
View article: Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens
Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens Open
Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases requires precision diagnostics, especially in c…