A5024826816- Photochromic and Fluorescence Chemistry
- Photoreceptor and optogenetics research
- Receptor Mechanisms and Signaling
- Nanoplatforms for cancer theranostics
- Retinal Development and Disorders
- Olfactory and Sensory Function Studies
- Neurobiology and Insect Physiology Research
- Photosynthetic Processes and Mechanisms
- Sleep and Wakefulness Research
- ATP Synthase and ATPases Research
- Cancer, Stress, Anesthesia, and Immune Response
- Spectroscopy and Quantum Chemical Studies
- Circadian rhythm and melatonin
- bioluminescence and chemiluminescence research
- Analytical Chemistry and Sensors
- Zebrafish Biomedical Research Applications
- Synthesis of Indole Derivatives
- Electrochemical sensors and biosensors
- Biomarkers in Disease Mechanisms
- Apelin-related biomedical research
- Porphyrin and Phthalocyanine Chemistry
- Inflammatory mediators and NSAID effects
- Human Health and Disease
- Oxidative Organic Chemistry Reactions
- Free Radicals and Antioxidants
Institute for Bioengineering of Catalonia
2018-2024
Barcelona Institute for Science and Technology
2018-2024
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine
2018-2024
Instituto de Salud Carlos III
2022-2024
Institute of Science and Technology
2019-2020
Shanghai Institute for Science of Science
2020
Universitat de Barcelona
2020
The efficacy and tolerability of systemically administered anticancer agents are limited by their off-target effects. Precise spatiotemporal control over cytotoxic activity would allow improving chemotherapy treatments, light-regulated drugs well suited to this purpose. We have developed phototrexate, the first photoswitchable inhibitor human dihydrofolate reductase (DHFR), as a photochromic analogue methotrexate, widely prescribed chemotherapeutic drug treat cancer psoriasis. Quantification...
Light-triggered reversible modulation of physiological functions offers the promise enabling on-demand spatiotemporally controlled therapeutic interventions. Optogenetics has been successfully implemented in heart, but significant barriers to its use clinic remain, such as need for genetic transfection. Herein, we present a method modulate cardiac function with light through photoswitchable compound and without manipulation. The molecule, named PAI, was designed by introduction photoswitch...
Adrenoceptors are ubiquitous and mediate important autonomic functions as well modulating arousal, cognition, pain on a central level. Understanding these physiological processes their underlying neural circuits requires manipulating adrenergic neurotransmission with high spatio-temporal precision. Here we present first generation of photochromic ligands (adrenoswitches) obtained via azologization class cyclic amidines related to the known ligand clonidine. Their pharmacology, photochromism,...
Background and Purpose Anion‐selective Cys‐loop receptors (GABA glycine receptors) provide the main inhibitory drive in CNS. Both types of receptor operate via chloride‐selective ion channels, though with different kinetics, pharmacological profiles, localization. Disequilibrium their function leads to a variety disorders, which are often treated allosteric modulators. The few available GABA channel blockers effectively suppress currents neurons, but systemic administration is highly toxic....
A problem of systemic pharmacotherapy is off-target activity, which causes adverse effects. Outstanding examples include neuroinhibitory medications like antiseizure drugs, are used against epilepsy and neuropathic pain but cause side There a need drugs that inhibit nerve signals locally on-demand without affecting other regions the body. Photopharmacology aims to address this with light-activated localized illumination in target organ. Here, we have developed photoswitchable derivatives...
Abstract Optogenetic and photopharmacological tools to manipulate neuronal inhibition have limited efficacy reversibility. We report the design, synthesis, biological evaluation of Fulgazepam, a fulgimide derivative benzodiazepine that behaves as pure potentiator ionotropic γ‐aminobutyric acid receptors (GABA A Rs) displays full reversible photoswitching in vitro vivo. The compound enables high‐resolution studies GABAergic neurotransmission, phototherapies based on localized, acute, neuroinhibition.
Abstract It has been recently shown that electron transfer between mitochondrial cytochrome c and the 1 subunit of bc can proceed at long-distance through aqueous solution. Cytochrome is thought to adjust its activity by changing affinity for partners via Tyr48 phosphorylation, but it unknown how impacts nanoscopic environment, interaction forces, long-range transfer. Here, we constrain orientation separation or phosphomimetic Y48 p CMF , deploy an array single-molecule, bulk, computational...
Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved modulation of fundamental physiological functions, dysregulation transmission associated with major neurological disorders. However, available tools to dissect endogenous circuits have limited specificity, reversibility, resolution, or require genetic manipulation. Here, we introduce azodopa, novel photoswitchable ligand that enables reversible spatiotemporal control...
Electron transfer (ET) between redox proteins is an essential process in the respiratory and photosynthetic transport chains. While intra-protein ET well characterized, experimental methods to investigate inter-protein are limited by presence of solvent transient nature protein-protein interaction event, which averaged protein ensembles. Wiring precisely oriented partners nanoscale electrodes electrochemical scanning tunneling microscope allows record time- distance-dependence current...
Photopharmacology is a unique approach that through combination of photochemistry methods and advanced life science techniques allows the study control specific biological processes, ranging from intracellular pathways to brain circuits. Recently, first photochromic channel blocker anion-selective GABAA receptors, azobenzene-nitrazepam-based compound (Azo-NZ1), has been described. In present study, using patch-clamp technique in heterologous system mice slices, site-directed mutagenesis...
We've combined the pharmacological properties of dynamin inhibitor dynasore and photochromic an azobenzene group, to obtain first light-regulated small-molecule endocytosis.
Abstract Adrenoceptors are ubiquitous and mediate important autonomic functions as well modulating arousal, cognition, pain on a central level. Understanding these physiological processes their underlying neural circuits requires manipulating adrenergic neurotransmission with high spatio‐temporal precision. Here we present first generation of photochromic ligands (adrenoswitches) obtained via azologization class cyclic amidines related to the known ligand clonidine. Their pharmacology,...
Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved modulation of fundamental physiological functions dysregulation transmission associated with major neurological disorders. However, available tools to dissect endogenous circuits have limited specificity, reversibility, resolution, or require genetic manipulation. Here we introduce azodopa, novel photoswitchable ligand that enables reversible spatiotemporal control...
Abstract A problem of systemic pharmacotherapy is off‐target activity, which causes adverse effects. Outstanding examples include neuroinhibitory medications like antiseizure drugs, are used against epilepsy and neuropathic pain but cause side There a need drugs that inhibit nerve signals locally on‐demand without affecting other regions the body. Photopharmacology aims to address this with light‐activated localized illumination in target organ. Here, we have developed photoswitchable...
Orexinergic neurons are critically involved in regulating arousal, wakefulness, and appetite. Their dysfunction has been associated with sleeping disorders, non-peptide drugs currently being developed to treat insomnia narcolepsy. Yet, no light-regulated agents available reversibly control their activity. To meet this need, a photoswitchable peptide analogue of the endogenous neuroexcitatory orexin-B was designed, synthesized, tested vitro vivo. This compound - photorexin is first...
Orexinergic neurons are critically involved in regulating arousal, wakefulness, and appetite. Their dysfunction has been associated with sleeping disorders, non-peptide drugs currently being developed to treat insomnia narcolepsy. Yet, no light-regulated agents available reversibly control their activity. To meet this need, a photoswitchable peptide analogue of the endogenous neuroexcitatory orexin-B was designed, synthesized, tested vitro vivo. This compound (photorexin) is first...
Adrenoceptors are ubiquitous and regulate heart respiratory rate, digestion, metabolism, vascular tone. They can be activated or blocked with adrenergic drugs, but systemic administration causes broad adverse effects. We have developed photochromic ligands (adrenoswitches) to switch on off adrenoceptor activity demand at selected locations. Their pharmacology, photochromism, bioavailability lack of toxicity allow photomodulating signalling, as demonstrated by controlling locomotion in...
Although cytotoxic chemotherapy is one of the primary pharmacological treatments for chronic hyperproliferative diseases such as cancer and psoriasis, its efficacy tolerability are in many cases dramatically limited by off-target toxicity. A promising approach to improve these therapies activate drugs exclusively at their desired place action. In fact, those that would benefit from a highly localized treatment, precise spatiotemporal control over activity chemotherapeutic agent allow...
ABSTRACT Glycine receptors (GlyRs) are indispensable to maintain excitatory/inhibitory balance in neuronal circuits controlling reflex and rhythmic motor behaviors. Here we have developed Glyght, the first GlyR ligand controlled with light. It is selective over other cys-loop receptors, active vivo , displays an allosteric mechanism of action. The photomanipulation glycinergic neurotransmission opens new avenues understand inhibitory intact animals, develop drug-based phototherapies.
<p>Remote control of physiological functions with light offers the promise unveiling their complex spatiotemporal dynamics in vivo, and enabling highly focalized therapeutic interventions reduced systemic toxicity. Optogenetic methods have been implemented heart, but need genetic manipulation jeopardizes clinical applicability. This study aims at developing, testing validating first light-regulated drug cardiac effects, order to avoid requirement offered by optogenetic methods. A M2...