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1.
Artificial cerebrospinal fluid (c.s.f.) containing 40 mmol/L excess calcium was perfus-ed through the lateral ventricles of New Zealand white rabbits in order to reduce the Na~+/Ca~(++) ratio in the brain and the effects on both the febrile response and adenosine cyclic mo-nophosphate (cAMP) concentration in plasma and c.s.f, during leucocytic pyrogen (LP)-induced fever were observed. The results showed that cAMP concentration in c.s.f, increas-ed significantly during LP-induced fever while the cAMP level in Plasma remained unchang-ed, and the perfusion of artificial c.s,f, containing 40 mmol/L excess calcium can signif-icantly inhibit not only the febrile response but also the increase in c.s.f, cAMP level,while there appears no effect on plasma cAMP concentration, thus demonstrating that theincrease of Na~+/Ca~(++) ratio causing the increase of cAMP content in the brain may be anessential link in the pathogenesis of LP-induced fever. 相似文献
2.
Bhattacharya S Schiavone M Nayak A Bhattacharya SK 《Applied biochemistry and biotechnology》2005,120(3):159-167
Our laboratory has recently developed a device employing immobilized F0F1 adenosine triphosphatase (ATPase) that allows synthesis of adenosine triphosphate (ATP) from adenosine 5′-diphosphate and
inorganic phosphate using solar energy. We present estimates of total solar energy received by Earth’s land area and demonstrate
that its efficient capture may allow conversion of solar energy and storage into bonds of biochemicals using devices harboring
either immobilized ATPase or NADH dehydrogenase. Capture and storage of solar energy into biochemicals may also enable fixation
of CO2 emanating from polluting units. The cofactors ATP and NADH synthesized using solar energy could be used for regeneration
of acceptor d-ribulose-1,5-bisphosphate from 3-phosphoglycerate formed during CO2 fixation. 相似文献
3.
Heat divided by ligand concentration vs. heat, similar to the Scatchard plot, was introduced to obtain the equilibrium constant
(K) and the enthalpy of binding (DH) using isothermal titration calorimetry data. Values of K and DH obtained by this linear
pseudo-Scatchard plot for a system with a set of independent binding sites (such as binding fluoride ions on urease and monosaccharide
methyl a-D-mannopyranoside on concavalin A) were remarkably like that obtained from a normal fitting Wiseman method and other
our technical methods. On applying this graphical method to study the binding of copper ion on myelin basic protein (MBP),
a concave downward curve obtained was consistent with the positive cooperativity in the binding. A graphical fitting by simple
method for determination of thermodynamic parameters was also introduced. This method is general, without any assumption and
restriction made in previous method. This general method was applied to the product inhibition study of adenosine deaminase.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
4.
Chenlin Feng Xuesong Wang Willem Jespers Rongfang Liu Sofía Denise Zamarbide Losada Marina Gorostiola Gonzlez Gerard J. P. van Westen Erik H. J. Danen Laura H. Heitman 《Molecules (Basel, Switzerland)》2022,27(15)
The adenosine A2A receptor (A2AAR) is a class A G-protein-coupled receptor (GPCR). It is an immune checkpoint in the tumor micro-environment and has become an emerging target for cancer treatment. In this study, we aimed to explore the effects of cancer-patient-derived A2AAR mutations on ligand binding and receptor functions. The wild-type A2AAR and 15 mutants identified by Genomic Data Commons (GDC) in human cancers were expressed in HEK293T cells. Firstly, we found that the binding affinity for agonist NECA was decreased in six mutants but increased for the V275A mutant. Mutations A165V and A265V decreased the binding affinity for antagonist ZM241385. Secondly, we found that the potency of NECA (EC50) in an impedance-based cell-morphology assay was mostly correlated with the binding affinity for the different mutants. Moreover, S132L and H278N were found to shift the A2AAR towards the inactive state. Importantly, we found that ZM241385 could not inhibit the activation of V275A and P285L stimulated by NECA. Taken together, the cancer-associated mutations of A2AAR modulated ligand binding and receptor functions. This study provides fundamental insights into the structure–activity relationship of the A2AAR and provides insights for A2AAR-related personalized treatment in cancer. 相似文献
5.
Purine 3′:5′‐cyclic nucleotides are very well known for their role as the secondary messengers in hormone action and cellular signal transduction. Nonetheless, their solid‐state conformational details still require investigation. Five crystals containing purine 3′:5′‐cyclic nucleotides have been obtained and structurally characterized, namely adenosine 3′:5′‐cyclic phosphate dihydrate, C10H12N5O6P·2H2O or cAMP·2H2O, (I), adenosine 3′:5′‐cyclic phosphate 0.3‐hydrate, C10H12N5O6P·0.3H2O or cAMP·0.3H2O, (II), guanosine 3′:5′‐cyclic phosphate pentahydrate, C10H12N5O7P·5H2O or cGMP·5H2O, (III), sodium guanosine 3′:5′‐cyclic phosphate tetrahydrate, Na+·C10H11N5O7P−·4H2O or Na(cGMP)·4H2O, (IV), and sodium inosine 3′:5′‐cyclic phosphate tetrahydrate, Na+·C10H10N4O7P−·4H2O or Na(cIMP)·4H2O, (V). Most of the cyclic nucleotide zwitterions/anions [two from four cAMP present in total in (I) and (II), cGMP in (III), cGMP− in (IV) and cIMP− in (V)] are syn conformers about the N‐glycosidic bond, and this nucleobase arrangement is accompanied by Crib—H…Npur hydrogen bonds (rib = ribose and pur = purine). The base orientation is tuned by the ribose pucker. An analysis of data obtained from the Cambridge Structural Database made in the context of syn–anti conformational preferences has revealed that among the syn conformers of various purine nucleotides, cyclic nucleotides and dinucleotides predominate significantly. The interactions stabilizing the syn conformation have been indicated. The inter‐nucleotide contacts in (I)–(V) have been systematized in terms of the chemical groups involved. All five structures display three‐dimensional hydrogen‐bonded networks. 相似文献
6.
A highly sensitive nanomechanical cantilever sensor assay based on an electrical measurement has been developed for detecting activated cyclic adenosine monophosphate (cyclic AMP)-dependent protein kinase (PKA). Employing a peptide derived from the heat-stable protein kinase inhibitor (PKI), a magnetic bead system was first selected as a vehicle to immobilize the PKI-(5-24) peptide for capturing PKA catalytic subunit and the activity assay was applied for indirectly assessing the binding. Synergistic interactions of adenosine triphosphate (ATP) and the peptide inhibitor with the kinase were then investigated by a solution phase capillary electrophoretic assay, and by surface plasmon resonance technology which involved immobilization of the peptide inhibitor. After systemically evaluated by a homogeneous direct binding assay, the ATP-dependent recognition of the catalytic subunit of PKA by PKI-(5-24) was successfully transferred on to the nanomechanical cantilevers at protein concentrations of 6.6 pM-66 nM, exhibiting much higher sensitivity and wider dynamic range than the conventional activity assay. Thus, direct assessment of activated kinases using the cantilever sensor system functionalized with specific peptide inhibitors holds great promise in analytical applications and clinical medicine. 相似文献
7.
Jinsu Bae Yeo-Ok Kim Xuehao Han Myung-Ha Yoon Woong-Mo Kim Yong-Chul Kim 《Molecules (Basel, Switzerland)》2022,27(4)
P2X3 receptors (P2X3R) are ATP-gated ion channels predominantly expressed in C- and Aδ-fiber primary afferent neurons and have been introduced as a novel therapeutic target for neurological disorders, including neuropathic pain and chronic cough. Because of its localized distribution, antagonism of P2X3R has been thoroughly considered, and the avoidance of issues related to CNS side effects has been proven in clinical trials. In this article, benzimidazole-4,7-dione-based derivatives were introduced as a new chemical entity for the development of P2X3R antagonists. Starting from the discovery of a hit compound from the screening of 8364 random library compounds in the Korea Chemical Bank, which had an IC50 value of 1030 nM, studies of structure–activity and structure–property relationships enabled further optimization toward improving the antagonistic activities as well as the drug’s physicochemical properties, including metabolic stability. As for the results, the final optimized compound 14h was developed with an IC50 value of 375 nM at P2X3R with more than 23-fold selectivity versus P2X2/3R, along with properties of metabolic stability and improved solubility. In neuropathic pain animal models evoked by either nerve ligation or chemotherapeutics in male Sprague-Dawley rats, compound 14h showed anti-nociceptive effects through an increase in the mechanical withdrawal threshold as measured by von Frey filament following intravenous administration. 相似文献
8.
Elisabetta Coppi Federica Cherchi Martina Venturini Elena Lucarini Renato Corradetti Lorenzo Di Cesare Mannelli Carla Ghelardini Felicita Pedata Anna Maria Pugliese 《Molecules (Basel, Switzerland)》2022,27(6)
Ligands of the Gi protein-coupled adenosine A3 receptor (A3R) are receiving increasing interest as attractive therapeutic tools for the treatment of a number of pathological conditions of the central and peripheral nervous systems (CNS and PNS, respectively). Their safe pharmacological profiles emerging from clinical trials on different pathologies (e.g., rheumatoid arthritis, psoriasis and fatty liver diseases) confer a realistic translational potential to these compounds, thus encouraging the investigation of highly selective agonists and antagonists of A3R. The present review summarizes information on the effect of latest-generation A3R ligands, not yet available in commerce, obtained by using different in vitro and in vivo models of various PNS- or CNS-related disorders. This review places particular focus on brain ischemia insults and colitis, where the prototypical A3R agonist, Cl-IB-MECA, and antagonist, MRS1523, have been used in research studies as reference compounds to explore the effects of latest-generation ligands on this receptor. The advantages and weaknesses of these compounds in terms of therapeutic potential are discussed. 相似文献
9.
10.
W. Russ Algar 《Analytica chimica acta》2010,673(1):1-25
A comprehensive review of the development of assays, bioprobes, and biosensors using quantum dots (QDs) as integrated components is presented. In contrast to a QD that is selectively introduced as a label, an integrated QD is one that is present in a system throughout a bioanalysis, and simultaneously has a role in transduction and as a scaffold for biorecognition. Through a diverse array of coatings and bioconjugation strategies, it is possible to use QDs as a scaffold for biorecognition events. The modulation of QD luminescence provides the opportunity for the transduction of these events via fluorescence resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET), charge transfer quenching, and electrochemiluminescence (ECL). An overview of the basic concepts and principles underlying the use of QDs with each of these transduction methods is provided, along with many examples of their application in biological sensing. The latter include: the detection of small molecules using enzyme-linked methods, or using aptamers as affinity probes; the detection of proteins via immunoassays or aptamers; nucleic acid hybridization assays; and assays for protease or nuclease activity. Strategies for multiplexed detection are highlighted among these examples. Although the majority of developments to date have been in vitro, QD-based methods for ex vivo biological sensing are emerging. Some special attention is given to the development of solid-phase assays, which offer certain advantages over their solution-phase counterparts. 相似文献