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1.
Artigo em Inglês | MEDLINE | ID: mdl-38656473

RESUMO

A Gram-stain-negative, aerobic, oxidase-positive, weakly catalase-positive, motile by means of a single polar flagellum, rod-shaped bacterium designated as strain S2-9T was isolated from sediment sampled in Wiyang pond, Republic of Korea. Growth of this strain was observed at 10-40 °C (optimum, 35 °C) and pH 5.5-9.5 (optimum, pH 7.0-8.0) and in the presence of 0-0.5 % NaCl in Reasoner's 2A broth. The major fatty acids (>10 %) of strain S2-9T were C16 : 0 and summed feature 3 (comprising a mixture of C16 : 1 ω7c and/or C16 : 1 ω6c). Ubiquinone-8 was detected as the respiratory quinone. The major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. Strain S2-9T showed the highest 16S rRNA gene sequence similarity to Paucibacter oligotrophus CHU3T (98.7 %), followed by 'Paucibacter aquatile' CR182 (98.4 %), all type strains of Pelomonas species (98.1-98.3 %), Mitsuaria chitosanitabida NBRC 102408T (97.9 %), Kinneretia asaccharophila KIN192T (97.8 %), Mitsuaria chitinivorans HWN-4T (97.4 %), and Paucibacter toxinivorans 2C20T (97.4 %). Phylogenetic trees based on the 16S rRNA gene and whole-genome sequences showed that strain S2-9T formed a tight phylogenetic lineage with Paucibacter species (CHU3T, CR182, and 2C20T). Average nucleotide identity and digital DNA-DNA hybridization values between strain S2-9T and Paucibacter strains were 76.6-79.3% and 19.5-21.5 %, respectively. The genomic DNA G+C content of strain S2-9T was 68.3 mol%. Notably, genes responsible for both sulphur oxidation and reduction and denitrification were found in the genome of strain S2-9T, suggesting that strain S2-9T is involved in the nitrogen and sulphur cycles in pond ecosystems. Based on the polyphasic taxonomic results, strain S2-9T represents a novel species of the genus Paucibacter, for which the name Paucibacter sediminis sp. nov. is proposed. The type strain is S2-9T (= KACC 22267T= JCM 34541T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Filogenia , Lagoas , RNA Ribossômico 16S , Análise de Sequência de DNA , Ubiquinona , Ácidos Graxos/análise , RNA Ribossômico 16S/genética , Sedimentos Geológicos/microbiologia , Lagoas/microbiologia , DNA Bacteriano/genética , República da Coreia , Hibridização de Ácido Nucleico
2.
Foods ; 12(11)2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37297390

RESUMO

The study investigated the antioxidant effects of roasted Cudrania tricuspidata (C. tricuspidata) fruits by comparing them with unroasted C. tricuspidata fruits. The results showed that the roasted C. tricuspidata fruits (150 °C, 120 min) exhibited significantly higher antioxidant activity, especially in terms of anti-inflammatory effects, than the unroasted fruits. Interestingly, there is a high correlation between the color of the roasted fruit and the antioxidant activity. Heating disrupts cells and deactivates endogenous oxidative enzymes, leading to an increase in flavonoid content. Moreover, heat treatment may also interfere with plant metabolism, thereby influencing flavonoid content. Moreover, an HPLC analysis of roasted fruits in our study showed that the increase in antioxidant activity was attributed to the increase in flavan-3-ols and phenolic acids in the roasted C. tricuspidata fruits. To the best of our knowledge, this is the first time the antioxidant activity and anti-inflammation of roasted C. tricuspidata fruits was studied. The study concluded that roasted C. tricuspidata fruits could be a valuable natural source of antioxidants for various food and medicinal applications.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36940160

RESUMO

A Gram-stain-negative, strictly aerobic, oxidase-positive, catalase-negative, motile by gliding, creamy white-pigmented bacterium, designated strain S2-8T, isolated from a sediment sample from a Wiyang pond in the Republic of Korea, was subjected to polyphasic taxonomic analysis. Growth was observed at 10-40 °C (optimum: 30 °C), pH 7-8 and 0-0.5% NaCl. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain S2-8T belonged to the family Sphingobacteriaceae in the phylum Bacteroidota and was closely related to Solitalea longa HR-AVT, Solitalea canadensis DSM 3403T and Solitalea koreensis R2A36-4T with 97.2, 96.7 and 93.7 % 16S rRNA gene sequence similarities, respectively. Average nucleotide identity and digital DNA-DNA hybridization values for these type strains were 72.0-75.2% and 21.2-21.9 %, respectively. The major respiratory quinone is menaquinone-7. The major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c). The major polar lipids were phosphatidylethanolamine, two unidentified amino acids and four unidentified lipids. The G+C content of genomic DNA was 37.9 mol%. Based on polyphasic taxonomic analysis, it was observed that strain S2-8T is a novel species belonging to the genus Solitalea, for which the name Solitalea lacus sp. nov. is proposed. The type strain is S2-8T (= KACC 22266T= JCM 34533T).


Assuntos
Ácidos Graxos , Lagoas , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Vitamina K 2/química
4.
J Microbiol Biotechnol ; 33(4): 449-462, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-36864505

RESUMO

Previously, we confirmed that Mychonastes sp. 246 methanolic extract (ME) markedly reduced the viability of BxPC-3 human pancreatic cancer cells. However, the underlying mechanism ME remained unclear. Hence, we attempted to elucidate the anticancer effect of ME on BxPC-3 human pancreatic cancer cells. First, we investigated the components of ME and their cytotoxicity in normal cells. Then, we confirmed the G1 phase arrest mediated growth inhibitory effect of ME using a cell counting assay and cell cycle analysis. Moreover, we found that the migration-inhibitory effect of ME using a Transwell migration assay. Through RNA sequencing, Gene Ontology-based network analysis, and western blotting, we explored the intracellular mechanisms of ME in BxPC-3 cells. ME modulated the intracellular energy metabolism-related pathway by altering the mRNA levels of IGFBP3 and PPARGC1A in BxPC-3 cells and reduced PI3K and mTOR phosphorylation by upregulating IGFBP3 and 4E-BP1 expression. Finally, we verified that ME reduced the growth of three-dimensional (3D) pancreatic cancer spheroids. Our study demonstrates that ME suppresses pancreatic cancer proliferation through the IGFBP3-PI3K-mTOR signaling pathway. This is the first study on the anticancer effect of the ME against pancreatic cancer, suggesting therapeutic possibilities and the underlying mechanism of ME action.


Assuntos
Neoplasias Pancreáticas , Fosfatidilinositol 3-Quinases , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células , Linhagem Celular Tumoral , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Apoptose , Movimento Celular/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/farmacologia , Neoplasias Pancreáticas
5.
Clin Oral Implants Res ; 34(2): 116-126, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36458928

RESUMO

BACKGROUND: The fixture thread depth reportedly influences the primary stability of dental implant, but its effect on the positional accuracy in immediate implant placement has not been reported previously. MATERIALS AND METHODS: Fifty-six single-rooted, anterior and premolar teeth were extracted from six human cadavers, followed by installing either regular-threaded implants (RT group, N = 30) or deep-threaded implants (DT group, N = 26) completely relying on the surgical guide. Optical impressions taken after osteotomy and fixture installation were superimposed with the preoperative virtual planning data to measure the vertical, angular, platform and apex deviations that occurred during osteotomy and installation. RESULTS: While the osteotomy deviations were similar between the two groups, the angular and apex deviation of the DT group (2.67 ± 2.56°; 1.04 ± 0.49 mm, respectively) were significantly larger than those of the RT group (1.61 ± 1.04°; 0.67 ± 0.41 mm, respectively) during installation (p < .05). When the installation deviations were analysed in the anterior and premolar areas separately, the angular, platform and apex deviations of the DT group (3.05 ± 3.26°; 0.75 ± 0.32 mm; 1.08 ± 0.56 mm, respectively) were significantly larger than those of the RT group (1.56 ± 0.73°, 0.59 ± 0.28 mm; 0.62 ± 0.38 mm, respectively) in the anterior site (p < .05), whereas there was no significant intergroup difference in the premolar site. CONCLUSION: In immediate-implant surgery, using an implant with a deeper thread might increase the deviations during installation, especially in the anterior area.


Assuntos
Implantes Dentários , Cirurgia Assistida por Computador , Humanos , Implantação Dentária Endóssea , Tomografia Computadorizada de Feixe Cônico , Cadáver , Desenho Assistido por Computador , Imageamento Tridimensional
6.
Artigo em Inglês | MEDLINE | ID: mdl-34824592

RESUMO

Essential oils are aromatic oils extracted from the leaves, stems, peels, petals, and roots of aromatic plants grown in nature or grown in organic methods and have various medical effects as natural substances. The essential oil extracted from Camellia japonica seeds exhibits various functional properties; however, its tyrosinase inhibitory activity has not been investigated extensively. This study is performed to investigate the chemical composition and tyrosinase inhibitory activity of Camellia japonica seed essential oil (CJS-EO). Hexamethylcyclotrisiloxane (42.36%) and octamethylcyclotetrasiloxane (23.28%) are the two primary components of CJS-EO, as identified via gas chromatography-mass spectrometry. The inhibitory activities of CJS-EO and positive control arbutin are further evaluated against mushroom tyrosinase. The results show that CJS-EO and arbutin inhibit tyrosinase activity. Moreover, CJS-EO significantly inhibits melanogenesis in the α-melanocyte-stimulating hormone-treated group, and a significant amount of melanin is suppressed. To ascertain the cause of the CJS-EO tyrosinase inhibitory effect and melanin reduction effect, genetic and protein analyses are performed. Based on our results, we tentatively conclude that CJS-EO can inhibit melanocytes from harmful factors such as tyrosinase-related protein. These results demonstrate that CJS-EO possesses potent antityrosinase activity and may be a good skin-whitening agent.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33502298

RESUMO

A Gram-positive, facultative anaerobic, catalase-negative, non-motile, non-spore-forming and rod-shaped lactic acid bacterium strain, denoted as NFFJ11T and isolated from total mixed fermentation feed in the Republic of Korea, was characterized through polyphasic approaches, including sequence analyses of the 16S rRNA gene and housekeeping genes (rpoA and pheS), determination of average nucleotide identity and in silico DNA-DNA hybridization, fatty acid methyl ester analysis, and phenotypic characterization. Phylogenetic analyses based on 16S rRNA, rpoA and pheS gene sequences revealed that strain NFFJ11T belonged to the genus Companilactobacillus. The 16S rRNA gene sequence of strain NFFJ11T exhibited high similarity to Companilactobacillus formosensis S215T (99.66 %), Companilactobacillus farciminis Rv4 naT (99.53 %), Companilactobacillus crustorum LMG 23699T (99.19 %), Companilactobacillus futsaii YM 0097T (99.06 %), Companilactobacillus zhachilii HBUAS52074T (98.86 %) and Companilactobacillus heilongiiangensis S4-3T (98.66 %). However, average nucleotide identity and in silico DNA-DNA hybridization values for these type strains were in the range of 79.90-92.93 % and 23.80-49.30 %, respectively, which offer evidence that strain NFFJ11T belongs to a novel species of the genus Companilactobacillus. The cell-wall peptidoglycan type was A4α (l-Lys-d-Asp) and the G+C content of the genomic DNA was 35.7 mol%. The main fatty acids of strain NFFJ11T were C18 : 1 ω9c (43.3 %), C16 : 0 (20.1 %) and summed feature 7 (18.3 %; comprising any combination of C19 : 1 ω7c, C19 : 1 ω6c and C19 : 0 cyclo ω10c). Through polyphasic taxonomic analysis, it was observed that strain NFFJ11T represents a novel species belonging to the genus Companilactobacillus, for which the name Companilactobacillus pabuli sp. nov. is proposed. The type strain is NFFJ11T (= KACC 21771T= JCM 34088T).

8.
Cell Rep ; 17(11): 3049-3061, 2016 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-27974216

RESUMO

While glial activation is an integral part of pain pathogenesis, the existence of a causal relationship between glia and pain processing has yet to be demonstrated in vivo. Here, we have investigated whether the activation of spinal astrocytes could directly evoke pain hypersensitivity in vivo via the use of optogenetic techniques. Optogenetic stimulation of channelrhopdopsin-2 (ChR)-expressing spinal astrocytes induced pain hypersensitivity in a reversible and time-dependent manner, which was accompanied by glial activation, NR1 phosphorylation, ATP release, and the production of proalgesic mediators. Photostimulation of ChR2-expressing astrocytes in culture and spinal slices recapitulated in vivo findings, demonstrating the release of proalgesic mediators and electrophysiological disinhibition of spinal projection neurons. These findings deepen our understanding of the role of astrocytes in pain pathogenesis and provide the scientific basis for an astrocyte-oriented pain treatment.


Assuntos
Astrócitos/metabolismo , Hipersensibilidade/genética , Dor/genética , Rodopsina/genética , Trifosfato de Adenosina/metabolismo , Astrócitos/patologia , Regulação da Expressão Gênica , Humanos , Hipersensibilidade/fisiopatologia , Proteínas do Tecido Nervoso/genética , Neuroglia/metabolismo , Neuroglia/fisiologia , Neurônios/metabolismo , Neurônios/patologia , Optogenética , Dor/fisiopatologia , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia
9.
Resuscitation ; 89: 195-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25541431

RESUMO

AIM: Tracheal intubation during cardiopulmonary resuscitation (CPR) is a high-risk procedure. Here, we investigated the efficacy of video laryngoscopy for tracheal intubation during CPR. METHODS: Data regarding tracheal intubation during CPR from in-hospital cardiac arrests occurring between January 2011 and December 2013 (n=229) were prospectively collected and retrospectively analyzed. RESULTS: The initial laryngoscopy method was video laryngoscopy in 121 patients (52.8%) and direct laryngoscopy in 108 patients (47.2%). The rate of successful intubation at the first attempt was higher with video laryngoscopy (71.9%; 87/121) than with direct laryngoscopy (52.8%; 57/108; p=0.003). The rate of success at the first attempt was higher for experienced (73.0%; 84/115) than inexperienced operators, including residents (52.6%; 60/114; p=0.001). Mortality at day 28 after CPR was not significantly different between patients with successful tracheal intubation at the first attempt and without (68.1% [98/144] vs. 67.1% [57/85]; p=0.876). In multivariate logistic regression analysis, a predicted difficult airway (odds ratio [95% confidence interval]=0.22 [0.10-0.49]; p<0.001), intubation by an experienced operator (2.63 [1.42-4.87]; p=0.002), and use of video laryngoscopy rather than direct laryngoscopy (2.42 [1.30-4.45]; p=0.005) were independently associated with a successful tracheal intubation at the first attempt. CONCLUSION: Use of video laryngoscopy during CPR from in-hospital cardiac arrest is independently associated with successful tracheal intubation at the first attempt.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca/terapia , Intubação Intratraqueal , Laringoscopia , Cirurgia Vídeoassistida , Idoso , Competência Clínica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos
10.
J Radiat Res ; 56(4): 717-26, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24927727

RESUMO

The aim of this study was to compare lateral photon-electron (LPE), helical tomotherapy (HT), and volumetric-modulated arc therapy (VMAT) plans for total scalp irradiation. We selected a single adult model case and compared the dosimetric results for the three plans. All plans mainly used 6-MV photon beams, and the prescription dose was 60 Gy in 30 fractions. First, we compared the LPE, HT and VMAT plans, with all plans including a 1-cm bolus. We also compared HT plans with and without the bolus. The conformity indices for LPE, HT and VMAT were 1.73, 1.35 and 1.49, respectively. The HT plan showed the best conformity and the LPE plan showed the worst. However, the plans had similar homogeneity indexes. The dose to the hippocampus was the highest in the VMAT plan, with a mean of 6.7 Gy, compared with 3.5 Gy in the LPE plan and 4.8 Gy in the HT plan. The doses to the optical structures were all within the clinically acceptable range. The beam-on time and monitor units were highest in the HT plan. The HT plans with and without a bolus showed similar target coverage and organ-at-risk (OAR) sparing. The HT plan showed the best target coverage and conformity, with low doses to the brain and hippocampus. This plan also had the advantage of not necessarily requiring a bolus. Although the VMAT plan showed better conformity than the LPE plan and acceptable OAR sparing, the dose to the hippocampus should be considered when high doses are prescribed.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Couro Cabeludo/efeitos da radiação , Neoplasias Cutâneas/radioterapia , Absorção de Radiação , Adulto , Feminino , Humanos , Tratamentos com Preservação do Órgão , Radiometria/métodos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
11.
J Radiat Res ; 55(1): 105-12, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23757513

RESUMO

Hypofractionated radiotherapy (HRT) is now commonly used for pulmonary malignancies, since a tumoricidal dose can be accurately delivered to the target without a consequential dose to adjacent normal tissues. However, radiation pneumonitis (RP) is still a major problem after HRT. To determine the significant parameters associated with developing RP, we retrospectively investigated data from patients with lung metastases treated with HRT using helical tomotherapy. A total of 45 patients were included in the study and the median age was 53 years old. The median prescriptive doses were 50 Gy to the internal target volume and 40 Gy to the planning target volume in 10 fractions over 2 weeks. RP was diagnosed by chest X-ray or computed tomography after HRT, and its severity was determined by CTCAE version 4.0. The incidence of symptomatic RP was 26.6%. Univariate analysis indicated that mean lung doses, V5, V10, V15, V20 and V25 were associated with the development of symptomatic RP (P < 0.05). However, multivariate analysis indicated that only V5 was associated with the development of symptomatic RP (P = 0.019). From the ROC curve, V5 was the most powerful predictor of symptomatic RP, and its AUC (area under curve) was 0.780 (P = 0.004). In addition, the threshold value of V5 for the development of symptomatic RP was 65%. A large distribution of low-dose radiation resulted in a higher risk of lung toxicity. So, to prevent symptomatic RP, it is recommended that the V5 be limited to <65%, in addition to considering conventional dosimetric factors. However, further clinical study must be undertaken in order to confirm this result.


Assuntos
Fracionamento da Dose de Radiação , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Pneumonite por Radiação/diagnóstico por imagem , Pneumonite por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pneumonite por Radiação/prevenção & controle , Radiografia , Radiometria , Espalhamento de Radiação , Resultado do Tratamento
12.
J Korean Acad Nurs ; 42(7): 1009-18, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23377597

RESUMO

PURPOSE: This study was done to evaluate effectiveness of home healthcare services (HHCS) specialized for elders who received spinal surgeries. METHODS: A non-equivalent control group pre-post test quasi-experimental study was performed. HHCS was developed based on the Rice model of dynamic self-determination for self-care. For data collection, a control group (n=23) and an experimental group (n=23) were selected by matching age, BMI, pain, general characteristics and type of spine surgery. Measurement tools to evaluate uncertainty and knowledge were developed by the authors. The Numeric Rating Scale (NRS) and Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were used to evaluate pain levels. Muscular strength in the legs was measured using a digital muscle tester and tape ruler. Questionnaires were used to evaluate disability in performing ADL and psychological distress levels. RESULTS: The experimental group showed significant decrease in uncertainty (p=.028), increased knowledge (p=.038), and partially decreased pain (p=.003-.331). Partial muscle strength increased significantly (p=.021-.644). Disability in performing ADL and psychological distress in the experimental group decreased significantly compared to control group (p=.002, p=.004). CONCLUSION: Results indicate HHCS is an efficient home care nursing program for these elders. Further experimental studies with larger samples are required to confirm effects of HHCS.


Assuntos
Pessoas com Deficiência/psicologia , Serviços de Saúde para Idosos/estatística & dados numéricos , Traumatismos da Coluna Vertebral/cirurgia , Atividades Cotidianas , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Medição da Dor , Escalas de Graduação Psiquiátrica , Estresse Psicológico , Inquéritos e Questionários , Incerteza
13.
Nucleosides Nucleotides Nucleic Acids ; 26(10-12): 1565-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18066827

RESUMO

On the basis of potent and selective binding affinity of Cl-IB-MECA to the human A(3) adenosine receptor, its 4'-thioadenosine derivatives were efficiently synthesized starting from D-gulonic gamma-lactone. Among compounds tested, 2-chloro-N(6)-(3-iodobenzyl)- and 2-chloro-N(6)-methyl-4' -thioadenosine-5' -methyluronamides (7a and 7b) exhibited nanomolar range of binding affinity (K(i) = 0.38 nM and 0.28 nM, respectively) at the human A(3)AR. These compounds showed anti-growth effects on HL-60 leukemia cell, which resulted from the inhibition of Wnt signaling pathway.


Assuntos
Agonistas do Receptor A3 de Adenosina , Adenosina/análogos & derivados , Antineoplásicos/química , Antineoplásicos/farmacologia , Tionucleosídeos/química , Tionucleosídeos/farmacologia , Adenosina/síntese química , Adenosina/química , Adenosina/farmacologia , Antineoplásicos/síntese química , Desenho de Fármacos , Células HL-60 , Humanos , Tionucleosídeos/síntese química , Proteínas Wnt/antagonistas & inibidores
14.
Artigo em Inglês | MEDLINE | ID: mdl-16880553

RESUMO

Clip-domain serine proteases (SPs) have been identified in invertebrates as crucial enzymes that are involved in diverse extracellular signalling pathways. Prophenoloxidase (proPO) activating factor-I (PPAF-I), a catalytically active clip-domain SP, cleaves proPO. To date, no crystal structures of a catalytically active clip-domain SP have been determined. Here, the results of crystallization and preliminary X-ray analysis of the SP domain of PPAF-I are reported. The crystal of the PPAF-I SP domain was obtained using the hanging-drop vapour-diffusion method in a precipitant solution containing 0.15 M lithium sulfate, 30% polyethylene glycol 4000 and 0.1 M Tris-HCl pH 8.0. The crystal diffracts X-rays to 1.7 angstroms resolution using a synchrotron-radiation source. The crystal belongs to space group P2(1)2(1)2(1), with one molecule in the asymmetric unit and unit-cell parameters a = 38.3, b = 53.3, c = 116.6 angstroms, alpha = beta = gamma = 90 degrees. A molecular-replacement solution has been found using kallikrein as a starting model, resulting in an interpretable electron-density map.


Assuntos
Catecol Oxidase/metabolismo , Precursores Enzimáticos/metabolismo , Serina Endopeptidases/química , Sequência de Aminoácidos , Domínio Catalítico , Sequência Conservada , Cristalografia por Raios X , Dados de Sequência Molecular , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Difração de Raios X
15.
Bioorg Med Chem ; 14(14): 4718-30, 2006 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-16603368

RESUMO

A large series of N6-substituted-4'-thioadenosines were synthesized starting from D-gulonic-gamma-lactone, and structure-activity relationships were studied at the human A3 and other subtypes of adenosine receptors (ARs). 2-Chloro-substituted and 2-H analogues were compared. 2-Chloro-N6-methyl-4'-thioadenosine 19b was a highly potent and selective agonist (Ki=0.8+/-0.1 nM in binding) at the A3AR, and displayed the same relative efficacy in receptor activation as a known full agonist, Cl-IB-MECA. Most of N6-substituted-4'-thioadenosines were less potent in binding than the corresponding N6-substituted-adenosines or N6-substituted-4'-thioadenosine-5'-uronamides. N6-(3-Iodobenzyl) derivative 19g was demonstrated to be an A3AR-selective partial agonist displaying a Ki value of 3.2 nM.


Assuntos
Agonistas do Receptor A3 de Adenosina , Adenosina/análogos & derivados , Tionucleosídeos/síntese química , Tionucleosídeos/farmacologia , Adenosina/síntese química , Adenosina/química , Adenosina/metabolismo , Adenosina/farmacologia , Animais , Células CHO , Cricetinae , AMP Cíclico/metabolismo , Desenho de Fármacos , Humanos , Técnicas In Vitro , Cinética , Ligantes , Espectroscopia de Ressonância Magnética , Receptor A1 de Adenosina/metabolismo , Receptor A2A de Adenosina/metabolismo , Proteínas Recombinantes/agonistas , Relação Estrutura-Atividade , Tionucleosídeos/química , Tionucleosídeos/metabolismo
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