A5103933230- Adenosine and Purinergic Signaling
- Pharmacological Receptor Mechanisms and Effects
- Receptor Mechanisms and Signaling
- Synthesis and Biological Evaluation
- Cardiac Ischemia and Reperfusion
- Retinal Diseases and Treatments
- Macrophage Migration Inhibitory Factor
- Glaucoma and retinal disorders
- Vector-borne infectious diseases
- Toxin Mechanisms and Immunotoxins
- Extracellular vesicles in disease
- Anesthesia and Neurotoxicity Research
- Chemical Synthesis and Analysis
- Micro and Nano Robotics
- Pharmacological Effects and Toxicity Studies
- Neurological Complications and Syndromes
- Phenothiazines and Benzothiazines Synthesis and Activities
- Streptococcal Infections and Treatments
- Botulinum Toxin and Related Neurological Disorders
- Neuroscience and Neuropharmacology Research
- Plant Pathogens and Fungal Diseases
- Peptidase Inhibition and Analysis
- Mycotoxins in Agriculture and Food
- Pneumocystis jirovecii pneumonia detection and treatment
- Mycorrhizal Fungi and Plant Interactions
University of Hertfordshire
2025
National Institutes of Health
2003-2024
National Institute of Diabetes and Digestive and Kidney Diseases
2010-2024
Shenyang Agricultural University
2020
Medical College of Wisconsin
2011
Seoul National University
2005
Max Planck Institute of Biochemistry
1988-1989
The recent determination of X-ray structures pharmacologically relevant GPCRs has made these targets accessible to structure-based ligand discovery. Here we explore whether novel chemotypes may be discovered for the A2A adenosine receptor, based on complementarity its recently determined structure. receptor signals in periphery and CNS, with agonists explored as anti-inflammatory drugs antagonists neurodegenerative diseases. We used molecular docking screen a 1.4 million compound database...
Abstract Phoma stem canker disease of oilseed rape ( Brassica napus ) is caused by the extracellular fungal pathogen Leptosphaeria maculans . Although this resides exclusively in apoplastic spaces surrounding plant cells, significance vesicles (EVs) has not been assessed. Here, we show a method to collect fluids (AFs) from infected leaves or cotyledons for collection EVs during process host colonisation. The 15,000 × g supernatants AFs were shown contain ribulose‐bisphosphate carboxylase...
Truncated N(6)-substituted-4'-oxo- and 4'-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A(2A) A(3) adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer palladium-catalyzed cross-coupling reactions utilized for functionalization of the position 6-chloropurine nucleosides. An unsubstituted 6-amino group a hydrophobic substituent required high affinity at hA(2A)AR, but abolished binding hA(2A)AR. However, most synthesized compounds...
The interaction of botulinum neurotoxins serotypes A, B and E (from Clostridium botulinum) tetanus neurotoxin tetani) with the surface liposomes made different lipid compositions was studied by photolabelling a radioiodinated photoactive phosphatidylethanolamine analogue [125I-dipalmitoyl (3,4-azidosalicylamido)phosphatidylethanolamine]. When vesicles were negatively charged lipids (asolectin), each these neurotoxic proteins radioiodinated, thus providing evidence for their attachment to...
Adenosine is increased in ischemic tissues where it serves a protective role by activating adenosine receptors (ARs), including the A<sub>3</sub> AR subtype. We investigated effect of <i>N</i>-{2-[(3,4-dichlorophenyl)amino]quinolin-4-yl}cyclohexanecarboxamide (LUF6096), positive allosteric modulator AR, on infarct size barbital-anesthetized dog model myocardial ischemia/reperfusion injury. Dogs were subjected to 60 min coronary artery occlusion and 3 h reperfusion. Infarct was assessed...
Truncated N(6)-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels corresponding 4'-thioadenosines. Hydrophobic N(6) and/or C2 substituents tolerated in A3AR binding, but only an unsubstituted 6-amino group a C2-hexynyl promoted high hA2AAR affinity. A small hydrophobic alkyl (4b and 4c) or N(6)-cycloalkyl (4d) showed excellent binding affinity at the hA3AR was better than free amino (4a). affinities of 3-halobenzylamine 4f-4i...
Potent and selective A3 adenosine receptor (AR) agonists were identified by the replacement of 4′-oxo- or 4′-thionucleosides with bioisosteric selenium. Unlike previous agonists, 4′-seleno analogues preferred a glycosidic syn conformation South sugar puckering, as shown in X-ray crystal structure 5′-N-methylcarbamoyl derivative 3p. Among compounds tested, N6-3-iodobenzyl analogue 3d was found to be most potent A3AR full agonist (Ki = 0.57 nM), which ≥800- 1900-fold for A1AR A2AAR,...
We have repurposed (N)-methanocarba adenosine derivatives (A3 receptor (AR) agonists) to enhance radioligand binding allosterically at the human dopamine (DA) transporter (DAT) and inhibit DA uptake. extended structure–activity relationship of this series with small N6-alkyl substitution, 5′-esters, deaza modifications adenine, ribose restored in place methanocarba. C2-(5-Halothien-2-yl)-ethynyl 5′-methyl 9 (MRS7292) 5′-ethyl 10 (MRS7232) esters enhanced DAT (EC50 ∼ 35 nM) norepinephrine...
The truncated C2- and C8-substituted-4'-thioadenosine derivatives 4a-d were synthesized from D-mannose, using palladium-catalyzed cross coupling reactions as key steps. In this study, an A(3) adenosine receptor (AR) antagonist, 4'-thioadenosine derivative 3 was successfully converted into a potent A(2A)AR agonist 4a (K(i) = 7.19 ± 0.6 nM) by appending 2-hexynyl group at the C2-position of that N(6)-substituted. However, C8-substitution greatly reduced binding affinity human A(2A)AR. All...
While screening off-target effects of rigid (N)-methanocarba-adenosine 5'-methylamides as A3 adenosine receptor (AR) agonists, we discovered μM binding hits at the δ-opioid (DOR) and translocator protein (TSPO). In an effort to increase OR decrease AR affinity by structure activity analysis this series, antagonist κ-(K)OR appeared in 5'-esters (ethyl 24 propyl 30), which retained TSPO interaction (μM). 7-Deaza modification C2-(arylethynyl)-5'-esters but not 4'-truncation enhanced KOR...
Tethered glycoconjugates of a naphthalene- and piperidine-containing antagonist the P2Y
The intact flagella of Wolinella succinogenes, a gram-negative, anaerobic bacterium with single polar flagellum, were obtained by an improved procedure, introduced recently Aizawa et al. (S.-J. Aizawa, G. E. Dean, C. J. Jones, R. M. Macnab, and S. Yamaguchi, Bacteriol. 161:836-849, 1985) for the flagellum Salmonella typhimurium. Disks diameter 130 +/- 30 nm, which attached to basal body isolated flagella, could be identified electron microscopy as additional structural elements bacterial...
Abstract Various series of 4,6‐disubstituted‐2‐thiopyridine derivatives were synthesized and evaluated as potential ecto‐5’‐nucleotidase (CD73) inhibitors. Altogether, about ninety compounds prepared using a general synthetic pathway involving one or two steps (eventually one‐pot) procedures. Variation the nature substituents in positions 4 6 (methyl, trifluoromethyl phenyl) thiopurine ring, well on thiol function, was examined led to marked differences both term reactivity ability interfere...
Maize [Zea mays L.] is an important food and feed crops in northeast of China. In 2019, maize seedling blight with incidence up to 25% was found at the field Fushun city Liaoning Province. Typical symptoms seedlings were yellow, thin, wilt die. The leaves gradually became yellow from base plant top. Root system poorly developed. primary roots usually discolored rotted. And faintly pink or puce-coloured mould on seeds rotted seedings. Symptomatic diseased collected surface-disinfested 70%...
4′-Thionucleoside derivatives as potent and selective A3 adenosine receptor agonists were synthesized, starting from d-gulono-γ-lactone via d-thioribosyl acetate a key intermediate, among which the 2-chloro-N6-methyladenosine-5′-methyluronamide showed most binding affinity (Ki=0.28±0.09 nM) at human receptor.