A photoresponsive system where structure formation is coupled to catalytic activity is presented. The observed catalytic activity is reliant on intermolecular cooperative effects that are present when amphiphiles assemble into vesicular structures. Photoresponsive units within the amphiphilic pre-catalysts allow for switching between assembled and disassembled states, thereby modulating the catalytic activity. The ability to reversibly form cooperative catalysts within a dynamic self-assembled system represents a conceptually new tool for the design of complex artificial systems in water.
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http://dx.doi.org/10.1002/anie.201907078 | DOI Listing |
Alzheimers Dement
December 2024
Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria.
Background: We identified small molecule tricyclic pyrone compound CP2 as a mild mitochondrial complex I (MCI) inhibitor that induces neuroprotection in multiple mouse models of AD. One of the major concerns while targeting mitochondria is the production of reactive oxygen species (ROS). CP2 consists of two diastereoisomers, D1 and D2, with distinct activity and toxicity profiles.
View Article and Find Full Text PDFAlzheimer's Disease (AD) is characterized by the amyloid plaques in patient brain. The plaques are formed by β-amyloid peptides (Aβs) that derive from the cleavage by γ-secretase. Over 300 AD pathogenic mutations have been identified in presenilin1/2 (PS1/PS2), the catalytic subunit of γ-secretase.
View Article and Find Full Text PDFBackground: Neurological disorders are at epidemic levels in the world today. Various proteins are being targeted for the development of novel molecular therapeutics; however, no small-molecule inhibitors have been discovered. Recent studies suggest that there are few molecules in clinical trials for various secretase (α, β, and γ), caspase, and calpain inhibitors.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Molecular Simulations and Design Group, Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106 Magdeburg, Germany.
Cezanne-2 (Cez2) is a deubiquitinylating (DUB) enzyme involved in the regulation of ubiquitin-driven cellular signaling and selectively targets Lys11-linked polyubiquitin chains. As a representative member of the ovarian tumor (OTU) subfamily DUBs, it performs cysteine proteolytic isopeptide bond cleavage; however, its exact catalytic mechanism is not yet resolved. In this work, we used different computational approaches to get molecular insights into the Cezanne-2 catalytic mechanism.
View Article and Find Full Text PDFArch Physiol Biochem
January 2025
Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway.
Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation of metabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscle energy metabolism, myotube cultures were established from and mice. Myotubes from mice had lower basal oleic acid and glucose oxidation compared to myotubes from mice.
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