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Photocontrolled trimethoprim PROTACs targeting the eDHFR protein tag Open
Proteolysis targeting chimeric small molecules (PROTACs) offer a strategy for degrading disease-associated proteins or controlling engineered protein tags fused to therapeutic proteins, like chimeric antigen receptors (CARs). New approache…
A prodrug targeting CIM6P/IGF2R enhances memory in healthy mice and reverses deficits in an Angelman syndrome mouse model Open
Devastating diseases of the central nervous system (CNS), such as neurodevelopmental disorders and neurodegenerative diseases, carry severe neurological symptoms, including cognitive impairment -a decline characterized by learning and memo…
Synthesis of Collinoketones via Biomimetic [6+4] Cycloaddition Open
Cycloadditions are among the most powerful reactions for constructing molecular complexity. The archetypal example is the [4+2] (Diels–Alder) cycloaddition, which efficiently furnishes cyclohexene derivatives. In comparison, the [6+4] cycl…
View article: Optical Control of Membrane Viscosity Modulates ER-to-Golgi Trafficking
Optical Control of Membrane Viscosity Modulates ER-to-Golgi Trafficking Open
The lipid composition of cellular membranes is highly dynamic and undergoes continuous remodeling, affecting the biophysical properties critical to biological function. Here, we introduce an optical approach to manipulate membrane viscosit…
Transient infrared nanoscopy resolves the millisecond photoswitching dynamics of single lipid vesicles in water Open
Understanding the biophysical and biochemical properties of molecular nanocarriers under physiological conditions with minimal interference is critical for advancing photopharmacology, drug delivery, nanotheranostics and synthetic biology.…
The Chemistry and Biology of the Tetrodotoxin Natural Product Family Open
Tetrodotoxin is a neurotoxic marine alkaloid, first isolated in 1909 from pufferfish and named after the biological order tetraodontiformes. Since its structural elucidation in 1964, it has attracted the interest of synthetic organic chemi…
Reversible Antagonism of Dopamine D1 Receptor using a Photoswitchable Remotely Tethered Ligand Open
Dopamine D1 receptor (D1R) plays key roles in health and disease. D1R is broadly expressed throughout the brain and body and is dynamically activated in response to endogenous dopamine, making it difficult to target this receptor with suff…
Spindle-localized F-actin regulates polar MTOC organization and the fidelity of meiotic spindle formation Open
Mammalian oocytes are notoriously prone to chromosome segregation errors leading to aneuploidy. The spindle provides the machinery for accurate chromosome segregation during cell division. Mammalian oocytes lack centrioles and, therefore, …
View article: Photoswitchable phospholipids for the optical control of membrane processes, protein function, and drug delivery
Photoswitchable phospholipids for the optical control of membrane processes, protein function, and drug delivery Open
Recent insights into the function and composition of cell membranes have transformed our understanding from primarily viewing these structures as passive barriers to recognizing them as dynamic entities actively involved in many cellular f…
Stereoselective Synthesis of Benzoylated Gulmirecin A and Disciformycin B Open
Disciformycins and gulmirecins are potent inhibitors of the bacterial RNA polymerase. They show promising activities against multidrug-resistant pathogens often found in clinical settings, such as methicillin- and vancomycin-resistant Stap…
The Chemistry and Biology of the Tetrodotoxin Natural Product Family Open
Tetrodotoxin is a neurotoxic marine alkaloid, first isolated in 1909 from pufferfish and named after the biological order tetraodontiformes. Since its structural elucidation in 1964, it has attracted the interest of synthetic organic chemi…
View article: Dopamine D1 receptor activation in the striatum is sufficient to drive reinforcement of anteceding cortical patterns
Dopamine D1 receptor activation in the striatum is sufficient to drive reinforcement of anteceding cortical patterns Open
Timed dopamine signals underlie reinforcement learning, favoring neural activity patterns that drive behaviors with positive outcomes. In the striatum, dopamine activates five dopamine receptors (D1R-D5R), which are differentially expresse…
Time-Lapse Super-Resolution Imaging and Optical Manipulation of Growth Cones in Elongating Axons and Migrating Neurons Open
The growth cone is a highly motile tip structure that guides axonal elongation and directionality in differentiating neurons. Migrating immature neurons also exhibit a growth cone-like structure (GCLS) at the tip of the leading process. Ho…
View article: An opioid efficacy switch for reversible optical control of peripheral analgesia
An opioid efficacy switch for reversible optical control of peripheral analgesia Open
The mu-opioid receptor (MOR) is a major target for the treatment of pain. However, opioids are prone to side effects which limit their effectiveness as analgesics and can lead to opioid use disorders or, even, lethal overdose. The systemic…
Biomimetic Synthesis of Azorellolide via Cyclopropylcarbinyl Cation Chemistry Open
A concise synthesis of the complex diterpene azorellolide, inspired by speculations on biosynthetic cationic cascades, is presented. The approach, guided by computation, relies on the intramolecular interception of a cyclopropylcarbinyl ca…
View article: Photoswitchable Diazocine Derivative for Adenosine A<sub>3</sub> Receptor Activation in Psoriasis
Photoswitchable Diazocine Derivative for Adenosine A<sub>3</sub> Receptor Activation in Psoriasis Open
Incorporating photoisomerizable moieties within drugs offers the possibility of rapid and reversible light-dependent switching between active and inactive configurations. Here, we developed a photoswitchable adenosine A3 receptor (A3R) ago…
Optical Control of TRPM8 Channels with Photoswitchable Menthol Open
Transient receptor potential melastatin 8 (TRPM8) channels are well known as sensors for cold temperatures and cooling agents such as menthol and icilin and these channels are tightly regulated by the membrane lipid phosphoinositol‐4,5‐bis…
View article: Concise Synthesis of (–)-Veratramine and (–)-20-epi-Veratramine via Aromative Diels-Alder Reaction
Concise Synthesis of (–)-Veratramine and (–)-20-epi-Veratramine via Aromative Diels-Alder Reaction Open
A concise and convergent synthesis of the isosteroidal alkaloids veratramine and 20-epi-veratramine has been accom-plished. A Horner-Wadsworth-Emmons olefination joins two chiral building blocks of approximately equal complexity and a tran…
View article: Concise Synthesis of (–)-Veratramine and (–)-20-epi-Veratramine via Aromative Diels-Alder Reaction
Concise Synthesis of (–)-Veratramine and (–)-20-epi-Veratramine via Aromative Diels-Alder Reaction Open
A concise and convergent synthesis of the isosteroidal alkaloids veratramine and 20-epi-veratramine has been accom-plished. A Horner-Wadsworth-Emmons olefination joins two chiral building blocks of approximately equal complexity and a tran…
Optical control of cardiac electrophysiology by the photochromic ligand azobupivacaine 2 Open
Background and Purpose Patients suffering from ischaemic heart disease and heart failure are at high risk of recurrent ventricular arrhythmias (VAs), eventually leading to sudden cardiac death. While high‐voltage shocks delivered by an imp…
View article: Neuroprotective effect of neuron‐specific deletion of the <scp>C16</scp> ceramide synthetic enzymes in an animal model of multiple sclerosis
Neuroprotective effect of neuron‐specific deletion of the <span>C16</span> ceramide synthetic enzymes in an animal model of multiple sclerosis Open
Ceramide C16 is a sphingolipid detected at high levels in several neurodegenerative disorders, including multiple sclerosis (MS). It can be generated de novo or from the hydrolysis of other sphingolipids, such as sphingomyelin or through t…
View article: Optical control of sphingolipid biosynthesis using photoswitchable sphingosines
Optical control of sphingolipid biosynthesis using photoswitchable sphingosines Open
Sphingolipid metabolism comprises a complex interconnected web of enzymes, metabolites and modes of regulation that influence a wide range of cellular and physiological processes. Deciphering the biological relevance of this network is cha…
Light-Activatable, Cell-Type Specific Labeling of the Nascent Proteome Open
Elucidating the mechanisms by which protein synthesis contributes to complex biological processes has remained a challenging endeavor. This is particularly true in the field of neuroscience, where multiple, tightly regulated periods of new…
Cell‐Specific Optical Control of AMPA Glutamate Receptors with a Photoswitchable Tethered Antagonist Open
AMPA receptors (AMPARs) are the main drivers of excitatory glutamatergic transmission in the brain, central to synaptic plasticity, and are key drug targets. However, AMPARs are expressed in virtually every neuron in the central nervous sy…
Transient infrared nanoscopy resolves the millisecond photoswitching dynamics of single lipid vesicles in water Open
Understanding the biophysical and biochemical properties of molecular nanocarriers under physiological conditions and with minimal interference is crucial for advancing nanomedicine, photopharmacology, drug delivery, nanotheranostics and s…