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Recent Advances in CBP/EP300 Degraders
Full text linkTargeted protein degradation (TPD) has emerged as an innovative therapeutic strategy, offering advantage over traditional approaches rooted in small-molecule inhibitors. Among the various modalities in TPD, proteolysis targeting chimeras (PROTACs) and molecular glue degraders (MGDs) have arisen as leading modalities, distinguished by their ability to induce protein degradation via the ubiquitin-proteasome system (UPS). In recent years, extensive research has focused on developing degraders targeting CREB-binding protein (CBP) and E1A-associated protein (EP300) – two homologous multidomain enzymes critical for enhancer-mediated transcription. This review explores the state of the art in CBP/EP300 degraders, underscoring the significant potential of these synthetic bifunctional compounds as innovative chemical tools and highly promising anticancer agents
Precision Probing of O-GalNAc Glycosylation Using Bump-and-Hole Engineering
Full text linkGlycosylation is a profound influencer of glycoprotein function. Glycans have a critical impact on health and disease, yet the tools to study them have trailed behind proteins and nucleic acids. O-GalNAc glycosylation involves the addition of N-acetylgalactosamine (GalNAc) to protein substrates. Dysregulation of O-GalNAc glycosylation is implicated in many pathologies such as cancer. Studying O-GalNAc glycosylation is complicated by the lack of a consensus sequence for initiation and the complex interdependence between a large family of 20 GalNAc transferases (GalNAc-Ts) in human cells. These issues necessitate precise methods of interrogating enzyme function. Herein, we discuss our own advances into the generation of precision tools to study O-GalNAc glycosylation and other glycosylation types. We discuss the use of bump-and-hole engineering to illuminate the roles of individual GalNAc-Ts. Engineering biosynthetic pathways enables cell line-specific uptake of chemical, editable sugars in co-culture settings. We provide an insight into the state-of-the-art in this field
Towards Biocompatible Cellulose Nanofiber Sponges with Tailored Pore Geometries
Full text linkCellulose nanofiber (CNF) sponges or CNF aerogels are promising biocompatible materials with applications ranging from biomedicine to environmental remediation. The highly porous architecture of these sponges – which is crucial for their functionality – is significantly influenced by the freezing step during fabrication. This review explores the critical role of freezing techniques in tailoring pore geometry and, consequently, the macroscopic properties of CNF sponges. We discuss conventional directional freezing methods and their limitations, highlighting the advantages of dynamic freezing for achieving isotropic pore structures. Furthermore, we examine various crosslinking strategies to enhance the stability and mechanical properties of CNF sponges. Finally, we present recent findings from our laboratory demonstrating the successful fabrication of biocompatible and crosslinked CNF sponges with tailored pore geometries using a dynamic freezing approach
Development of Flow Electrolytic Strategies for Separation and Radiometric Analysis of Radionuclides
Full text linkRadionuclides are used and produced for a variety of applications, such as in the framework of energy production and nuclear medicine. This requires appropriate monitoring which in turn translates into the analysis of a variety of radionuclides in demanding sample matrices. Radionuclide analysis is a challenging task and often requires complex chemical processing of the samples prior to radiometric measurements. This requirement arises due to interfering radionuclides as well as matrix elements, which typically prevent a direct measurement by α- and γ-spectrometry, liquid scintillation counting or mass spectrometry. Despite offering promising possibilities, electrochemical approaches have been rarely used so far for the separation and analysis of radionuclides. Here, we present the development of fast flow-through electrolytic separation approaches for the analysis of carrier-added/-free radionuclides in fundamental and applied research
Base Metal Meets Photoredox Chemistry – Advances in Fully Catalytic Metal-Catalyzed Hydrogen Atom Transfer Reactions
Full text linkMetal-catalyzed hydrogen atom transfer (MHAT) has become a valuable approach for the functionalization of alkenes and toward complex molecular structures. This review discusses recent advancements in the field, particularly the integration of metal catalysis with photoredox catalysis which obviates the need for sacrificial reagents. Key transformations, including heterocycle formation, olefin hydrofunctionalization, and semi-pinacol rearrangements are examined in detail, highlighting the potential of photo-MHAT for efficient and sustainable synthetic strategies
Kinetic Investigation of the Asymmetric Hydrogenation of Benzylphenylephrone in Continuous Flow
Full text linkIn the pharmaceutical industry, efficient, fast, and cost-effective API manufacturing processes are crucial for maintaining competitiveness. However, traditional production methods are often dominated by multi-purpose batch processes and empirical development approaches. This study presents the design and development of a fully automated, mL-scale continuous flow process for the asymmetric hydrogenation of benzylphenylephrone to (R)-benzylphenylephrine (BPE). The process employs a rhodium-based homogeneous catalyst under high pressure (up to 65 bar), achieving conversions of >96%, yields of up to 95% and high enantiomeric excess (ee) of up to 91%, with residence times of less than five minutes and a molar substrate to catalyst ratio (S/C) of 750. Kinetic investigations were conducted in a continuous flow microreactor, resulting in the development of a kinetic model that closely matches experimental data