Locked-Azobenzene: Testing the Scope of a Unique Photoswitchable Scaffold for Cell Physiology.


:Azobenzenes are the most widely studied photoswitches, and have become popular optical probes for biological systems. The cis configuration is normally metastable, meaning the trans configuration is always thermodynamically favored. The unique exception to this rule is an azobenzene having a two-carbon bridge between ortho positions, substitutions that lock the photoswitch in its cis configuration. Only thoroughly chemically characterized relatively recently, we describe the first applications of this locked-azobenzene (or "LAB") scaffold with two derivatives designed to control ion flow in pyramidal neurons in acutely isolated brain slices. Our LAB derivatives maintain most of the desirable photochemical properties of the parent scaffold, and work as designed in living cells. However, LAB derivitization changes the trans photostationary state from >85% of the parent photoswitch to about 50%, suggesting that careful design considerations must be given for future applications of the LAB scaffold in biological areas.


ACS Chem Neurosci


Thapaliya ER,Zhao J,Ellis-Davies GCR




Has Abstract


2019-05-15 00:00:00










  • An azobenzene photoswitch sheds light on turn nucleation in amyloid-β self-assembly.

    abstract::Amyloid-β (Aβ) self-assembly into cross-β amyloid fibrils is implicated in a causative role in Alzheimer's disease pathology. Uncertainties persist regarding the mechanisms of amyloid self-assembly and the role of metastable prefibrillar aggregates. Aβ fibrils feature a sheet-turn-sheet motif in the constituent β-stra...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Doran TM,Anderson EA,Latchney SE,Opanashuk LA,Nilsson BL

    更新日期:2012-03-21 00:00:00

  • An Engineered Variant of the B1 Domain of Protein G Suppresses the Aggregation and Toxicity of Intra- and Extracellular Aβ42.

    abstract::Intra- and extraneuronal deposition of amyloid β (Aβ) peptides have been linked to Alzheimer's disease (AD). While both intra- and extraneuronal Aβ deposits affect neuronal cell viability, the molecular mechanism by which these Aβ structures, especially when intraneuronal, do so is still not entirely understood. This ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Banerjee V,Oren O,Dagan B,Taube R,Engel S,Papo N

    更新日期:2019-03-20 00:00:00

  • Novel Disassembly Mechanisms of Sigmoid Aβ42 Protofibrils by Introduced Neutral and Charged Drug Molecules.

    abstract::Alzheimer's disease (AD) is characterized by fibrillar deposits of amyloid-β (Aβ) peptides and neurofibrillary tangles of Tau proteins. Aβ peptides are composed of 37-49 residues, among which the Aβ42 isoform is particularly toxic and aggregation-prone and is enriched in the plaques of AD brains and thus considered ce...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Xing X,Liu C,Ali A,Kang B,Li P,Ai H

    更新日期:2020-01-02 00:00:00

  • Fluorescent 1,4-Naphthoquinones To Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains.

    abstract::Recent clinical approvals of brain imaging radiotracers targeting amyloid-β provided clinicians the tools to detect and confirm Alzheimer's disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer's patients, there is much room for improvement in earlier diag...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Neo Shin N,Jeon H,Jung Y,Baek S,Lee S,Yoo HC,Bae GH,Park K,Yang SH,Han JM,Kim I,Kim Y

    更新日期:2019-06-19 00:00:00

  • Serotonin neuron diversity in the dorsal raphe.

    abstract::The dorsal raphe nucleus contains one of the largest groups of serotonergic neurons in the mammalian brain and is the main site of origin of the serotonergic projection to the cerebral cortex. Early electrophysiological studies suggested that serotonergic neurons in this cell group formed a homogeneous cell class. Mor...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审


    authors: Andrade R,Haj-Dahmane S

    更新日期:2013-01-16 00:00:00

  • Identifying New AMP-Activated Protein Kinase Inhibitors That Protect against Ischemic Brain Injury.

    abstract::We recently reported that AMP-activated protein kinase (AMPK) contributes to zinc-induced neuronal death by inducing Bim, a pro-apoptotic Bcl-2 homology domain 3-only protein, in a liver kinase B1 (LKB1)-dependent manner. Current data suggest AMPK plays key roles in excitotoxicity and ischemic brain injury, with zinc ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Eom JW,Kim TY,Seo BR,Park H,Koh JY,Kim YH

    更新日期:2019-05-15 00:00:00

  • Gut Microbiota Dynamics in Parkinsonian Mice.

    abstract::Peripheral immunity is thought to be dysregulated in Parkinson's disease (PD) and may provide an avenue for novel immunotherapeutic interventions. Gut microbiota is a potential factor for modulating immunotherapy response. Considering the possibly complex role of the gut-brain axis in PD, we used a preclinical model t...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Klann E,Tagliamonte MS,Ukhanova M,Mai V,Vedam-Mai V

    更新日期:2020-10-21 00:00:00

  • Synthesis, biophysical, and pharmacological evaluation of the melanocortin agonist AST3-88: modifications of peptide backbone at Trp 7 position lead to a potent, selective, and stable ligand of the melanocortin 4 receptor (MC4R).

    abstract::The melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors are expressed in the brain and are implicated in the regulation of food intake and energy homeostasis. The endogenous agonist ligands for these receptors (α-, β-, γ-MSH and ACTH) are linear peptides with limited receptor subtype selectivity and metabolic st...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Singh A,Dirain ML,Wilczynski A,Chen C,Gosnell BA,Levine AS,Edison AS,Haskell-Luevano C

    更新日期:2014-10-15 00:00:00

  • Amyloid-β Peptide-Lipid Bilayer Interaction Investigated by Supercritical Angle Fluorescence.

    abstract::The understanding of the interaction between the membrane of neurons and amyloid-β peptides is of crucial importance to shed light on the mechanism of toxicity in Alzheimer's disease. This paper describes how supercritical angle fluorescence spectroscopy was applied to monitor in real-time the interaction between a su...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Dubois V,Serrano D,Seeger S

    更新日期:2019-12-18 00:00:00

  • Recent progress on the identification of metabotropic glutamate 4 receptor ligands and their potential utility as CNS therapeutics.

    abstract::This Review describes recent activity in the advancement of ligands for the metabotropic glutamate 4 receptor subtype and their potential utility as central nervous system (CNS) therapeutics. Until recently, there was a paucity of compounds with suitable selectivity and druglike properties to elucidate the value of th...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审


    authors: Robichaud AJ,Engers DW,Lindsley CW,Hopkins CR

    更新日期:2011-08-17 00:00:00

  • D-serine uptake and release in PC-12 cells measured by chiral microchip electrophoresis-mass spectrometry.

    abstract::Previous work has established that D-serine (D-Ser) plays important roles in certain neurological processes. Study on its uptake/storage and release by neuronal cells is highly significant for elucidating relevant mechanisms. In this work, PC-12 cells were incubated with racemic Ser (100 μM each enantiomer). After inc...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Li X,McCullum C,Zhao S,Hu H,Liu YM

    更新日期:2015-04-15 00:00:00

  • A Small Molecule Mimetic of the Humanin Peptide as a Candidate for Modulating NMDA-Induced Neurotoxicity.

    abstract::Humanin (HN), a 24-amino acid bioactive peptide, has been shown to increase cell survival of neurons after exposure to Aβ and NMDA-induced toxicity and thus could be beneficial in the treatment of Alzheimer's disease (AD). The neuroprotection by HN is reported to be primarily through its agonist binding properties to ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Alam MP,Bilousova T,Spilman P,Vadivel K,Bai D,Elias CJ,Evseenko D,John V

    更新日期:2018-03-21 00:00:00

  • Amyloid-β Peptide Targeting Peptidomimetics for Prevention of Neurotoxicity.

    abstract::A new generation of ligands designed to interact with the α-helix/β-strand discordant region of the amyloid-β peptide (Aβ) and to counteract its oligomerization is presented. These ligands are designed to interact with and stabilize the Aβ central helix (residues 13-26) in an α-helical conformation with increased inte...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Honcharenko D,Juneja A,Roshan F,Maity J,Galán-Acosta L,Biverstål H,Hjorth E,Johansson J,Fisahn A,Nilsson L,Strömberg R

    更新日期:2019-03-20 00:00:00

  • Structure-selective anisotropy assay for amyloid Beta oligomers.

    abstract::Amyloid β (Abeta) peptides in their oligomeric form have been proposed as major toxic species in Alzheimer's disease (AD). There are a limited number of anti-Abeta antibodies specific to oligomeric forms of Abeta compared to the monomeric form, and accurate measurement of oligomeric forms in biological samples, cerebr...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Matveeva EG,Rudolph A,Moll JR,Thompson RB

    更新日期:2012-11-21 00:00:00

  • Involvement of protein kinase C in morphine tolerance at spinal levels of rats.

    abstract::The present study was performed to investigate the possible role of protein kinase C (PKC) in morphine tolerance at spinal levels of rats. Intrathecal injection of 10 μg of morphine induced increases in the hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation in rats. After intrathecal inject...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Jin WY,Yu LC

    更新日期:2010-02-17 00:00:00

  • Sowing the Seeds of Discovery: Tau-Propagation Models of Alzheimer's Disease.

    abstract::The propagation of pathological proteins throughout the brain is the primary physiological hallmark of the progression of Alzheimer's Disease (AD). A growing body of evidence indicates that hyperphosphorylated Tau proteins are spread transcellularly between neurons in a prionlike fashion, inducing misfolding and aggre...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Bell BJ,Malvankar MM,Tallon C,Slusher BS

    更新日期:2020-11-04 00:00:00

  • Bax Activation Blocks Self-Renewal and Induces Apoptosis of Human Glioblastoma Stem Cells.

    abstract::Glioblastoma (GBM) is characterized by a poor response to conventional chemotherapeutic agents, attributed to the insurgence of drug resistance mechanisms and to the presence of a subpopulation of glioma stem cells (GSCs). GBM cells and GSCs present, among others, an overexpression of antiapoptotic proteins and an inh...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Daniele S,Pietrobono D,Costa B,Giustiniano M,La Pietra V,Giacomelli C,La Regina G,Silvestri R,Taliani S,Trincavelli ML,Da Settimo F,Novellino E,Martini C,Marinelli L

    更新日期:2018-01-17 00:00:00

  • Increased Brain Exposure of an Alpha-Synuclein Fibrillization Modulator by Utilization of an Activated Ester Prodrug Strategy.

    abstract::Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha-synuclein (α-syn) fibrillization in vitro. As a first step toward developing molecules from this scaffold as positron emission tomography imaging agents, we were interested in evaluating their blood-...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Cairns AG,Vazquez-Romero A,Mahdi Moein M,Ådén J,Elmore CS,Takano A,Arakawa R,Varrone A,Almqvist F,Schou M

    更新日期:2018-11-21 00:00:00

  • Future Priorities in Tackling Infections Due to Brain-Eating Amoebae.

    abstract::Brain-eating amoebae (Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri) can cause opportunistic infections involving the central nervous system. It is troubling that the mortality rate is more than 90% despite advances in antimicrobial chemotherapy over the last few decades. Here, we describe urgent k...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Khan NA,Anwar A,Siddiqui R

    更新日期:2017-11-15 00:00:00

  • Proneurogenic Effects of Trazodone in Murine and Human Neural Progenitor Cells.

    abstract::Several antidepressants increase adult hippocampal neurogenesis (ahNG) in rodents, primates, and, potentially, humans. This effect may at least partially account for their therapeutic activity. The availability of antidepressants whose mechanism of action involves different neurotransmitter receptors represents an opp...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Bortolotto V,Mancini F,Mangano G,Salem R,Xia E,Del Grosso E,Bianchi M,Canonico PL,Polenzani L,Grilli M

    更新日期:2017-09-20 00:00:00

  • A Novel Negative Allosteric Modulator Selective for GluN2C/2D-Containing NMDA Receptors Inhibits Synaptic Transmission in Hippocampal Interneurons.

    abstract::N-Methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors that mediate excitatory synaptic transmission and have been implicated in numerous neurological disorders. NMDARs typically comprise two GluN1 and two GluN2 subunits. The four GluN2 subtypes (GluN2A-GluN2D) have distinct functional properties a...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Swanger SA,Vance KM,Acker TM,Zimmerman SS,DiRaddo JO,Myers SJ,Bundgaard C,Mosley CA,Summer SL,Menaldino DS,Jensen HS,Liotta DC,Traynelis SF

    更新日期:2018-02-21 00:00:00

  • Benzothiophene Selective Estrogen Receptor Modulators Provide Neuroprotection by a novel GPR30-dependent Mechanism.

    abstract::The clinical benzothiophene SERM (BT-SERM), raloxifene, was compared with estrogens in protection of primary rat neurons against oxygen-glucose deprivation (OGD). Structure-activity relationships for neuroprotection were determined for a family of BT-SERMs displaying a spectrum of ERα and ERβ binding affinity and agon...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Abdelhamid R,Luo J,Vandevrede L,Kundu I,Michalsen B,Litosh VA,Schiefer IT,Gherezghiher T,Yao P,Qin Z,Thatcher GR

    更新日期:2011-05-18 00:00:00

  • Neuromicrobiology: How Microbes Influence the Brain.

    abstract::We review here recent discoveries in the exciting new field of neuromicrobiology. This field encompasses the interactions between the microbiome and the central nervous system. The microbiome has a tremendous impact on human health. In particular, the gut microbiota may play a key role in many essential processes in h...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审


    authors: de la Fuente-Nunez C,Meneguetti BT,Franco OL,Lu TK

    更新日期:2018-02-21 00:00:00

  • Brain Targeting by Liposome-Biomolecular Corona Boosts Anticancer Efficacy of Temozolomide in Glioblastoma Cells.

    abstract::Temozolomide (TMZ) is the current first-line chemotherapy for treatment of glioblastoma multiforme (GBM). However, similar to other brain therapeutic compounds, access of TMZ to brain tumors is impaired by the blood-brain barrier (BBB) leading to poor response for GBM patients. To overcome this major hurdle, we have s...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Arcella A,Palchetti S,Digiacomo L,Pozzi D,Capriotti AL,Frati L,Oliva MA,Tsaouli G,Rota R,Screpanti I,Mahmoudi M,Caracciolo G

    更新日期:2018-12-19 00:00:00

  • Evidence for an extracellular zinc-veneer in rodent brains from experiments with Zn-ionophores and ZnT3 knockouts.

    abstract::Ionic zinc is found at a high concentration in some glutamatergic vesicles of the mammalian brain. Ionic zinc is also found chelated to macromolecules in the extracellular space, constituting what has been called the "zinc veneer". In this communication we show that the zinc ionophore, pyrithione, can be used to demon...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Nydegger I,Rumschik SM,Zhao J,Kay AR

    更新日期:2012-10-17 00:00:00

  • Neuron Activity Dependent Redox Compartmentation Revealed with a Second Generation Red-Shifted Ratiometric Sensor.

    abstract::Oxidative stress is a hallmark of several aging and trauma related neurological disorders, but the precise details of how altered neuronal activity elicits subcellular redox changes have remained difficult to resolve. Current redox sensitive dyes and fluorescent proteins can quantify spatially distinct changes in reac...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Radhakrishnan S,Norley J,Wendt S,LeRoy N,Hall H,Norcross S,Doan S,Snaider J,MacVicar BA,Weake VM,Huang L,Tantama M

    更新日期:2020-09-02 00:00:00

  • Interrogating the Molecular Basis for Substrate Recognition in Serotonin and Dopamine Transporters with High-Affinity Substrate-Based Bivalent Ligands.

    abstract::The transporters for the neurotransmitters serotonin and dopamine (SERT and DAT, respectively) are targets for drugs used in the treatment of mental disorders and widely used drugs of abuse. Studies of prokaryotic homologues have advanced our structural understanding of SERT and DAT, but it still remains enigmatic whe...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Andersen J,Ladefoged LK,Kristensen TN,Munro L,Grouleff J,Stuhr-Hansen N,Kristensen AS,Schiøtt B,Strømgaard K

    更新日期:2016-10-19 00:00:00

  • Modulation of Alzheimer's Aβ protofilament-membrane interactions by lipid headgroups.

    abstract::The molecular pathogenesis of Alzheimer's disease (AD) is complex and sparsely understood. The relationship between AD's amyloid β (Aβ) peptides and neuronal membranes is central to Aβ's cytotoxicity and is directly modulated by the composition of the lipid headgroups. Molecular studies of the insertion of model Aβ40 ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Tofoleanu F,Brooks BR,Buchete NV

    更新日期:2015-03-18 00:00:00

  • Behavioral and Biochemical Implications of Dendrimeric Rivastigmine in Memory-Deficit and Alzheimer's Induced Rodents.

    abstract::Exploration of dendrimers for effective drug delivery is giving promising results. The present study was designed and performed to explore the dendrimeric (polyamidoamine-lactoferrin; PAMAM-Lf) formulations for the effective rivastigmine (RIV) delivery against the Alzheimer's induced animal model using lactoferrin as ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Gothwal A,Singh H,Jain SK,Dutta A,Borah A,Gupta U

    更新日期:2019-08-21 00:00:00

  • AMPA Receptor Noncompetitive Inhibitors Occupy a Promiscuous Binding Site.

    abstract::Noncompetitive inhibitors of AMPA receptors have attracted interest in recent years as antiepileptic drugs. However, their development is hindered by a lack of detailed understanding of the protein-inhibitor interaction mechanisms. Recently, structures of AMPA receptor complexes with the structurally dissimilar, nonco...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章


    authors: Narangoda C,Sakipov SN,Kurnikova MG

    更新日期:2019-11-20 00:00:00