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1.
Food Chem ; 346: 128897, 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33406455

RESUMO

Pichia fermentans Z9Y-3 and its intracellular enzymes were inoculated along with S. cerevisiae in synthetic grape must to modulate fruity ester production. The levels of ester-related enzymes, ester precursors, and fruity esters were monitored every 24 h during fermentation. Results showed that the levels of ethyl acetate, acetate higher alcohol esters (AHEs), short chain fatty acid ethyl esters (SFEs), and medium chain fatty acid ethyl esters (MFEs) were significantly enhanced in mixed fermentation. Pearson correlation analysis further revealed that higher alcohols and fatty acids played a more important role in fruity ester production than enzymes; Particularly, the correlation coefficient between fatty acids and MFEs was 0.940. In addition, supplementation of medium chain fatty acids (7.2 mg/L) at the metaphase of single S. cerevisiae fermentation improved ethyl acetate, AHE, SFE, and MFE production by 42.56%, 21.00%, 61.33%, and 90.04%, respectively, although the high level of ethyl acetate might result in off-flavors.

2.
Int J Med Sci ; 18(1): 128-136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390781

RESUMO

Background: Traumatic brain injury (TBI) is a sudden trauma on the head, in which severe TBI (sTBI) is usually associated with death and long-term disability. MicroRNAs (miRNAs) are potential biomarkers of diverse diseases, including TBI. However, few systematic reviews and meta-analyses have been conducted to determine the clinical value of miRNAs expression in TBI patients. Methods: We conducted this systematic review and meta-analysis study according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Embase, the Cochrane Library, Web of Science, from inception to August 26, 2020. We included articles written in English that have reported on the diagnostic value of miRNAs expression in TBI patients. We excluded studies that did not provided sufficient information to construct the 2×2 contingency table. Results: Eight studies investigating the diagnostic value of miRNA in TBI were analyzed in this study. The overall sensitivity, specificity and area under the curve (AUC) of miRNAs in diagnosis of TBI were 89% [95% confidence interval (CI): 0.84-0.93], 92% (95% CI 0.82-0.97) and 95% (95% CI 0.93-0.97). We found that panels of multiple miRNAs could improve the diagnostic accuracy of TBI. Samples from blood and brain tissue have significantly enhanced diagnostic accuracy, when compared with saliva. The AUC of miRNAs in severe TBI was 0.97, with 91% sensitivity and 92% specificity. Conclusion: This systematic review and meta-analysis demonstrated that miRNAs could be potential diagnostic markers in TBI patients. MiRNAs detected in blood and brain tissue display high accuracy for TBI diagnosis.

3.
Neurotox Res ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33443646

RESUMO

Cerebrospinal fluid (CSF) progranulin (PGRN) is related to various neurodegeneration diseases. And sleep problems can cause abnormality in protein metabolism in vivo. We aim to explore the potential associations between the self-reported sleep characteristics and CSF PGRN in cognitively intact older adults. Our study recruited 747 participants (mean (standard deviation (SD)) age, 61.99 (10.52) years, 329 (42.89%) females) who had normal cognition from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study with CSF PGRN and sleep characteristics measured. The multiple linear regression and nonlinear regression adjusted for age, gender, education, and apolipoprotein E-epsilon 4 gene (APOE4) status were used to assess the associations between sleep characteristics and PGRN. Interaction effects were explored between APOE4 status and sleep characteristics on CSF PGRN level. Sleep disturbances indicated lower CSF PGRN (ß = - 0.0186, p = 0.0160). For detailed items in sleep disturbances, lower CSF PGRN was found in males who woke up during sleep (ß = - 0.0121, p = 0.0062) and in females who had breathing difficulties (ß = - 0.0258, p = 0.0271). Meanwhile, sleep efficiency was associated with CSF PGRN (ß = - 0.0512, p = 0.0497). No significant interaction effects between sleep characteristics and APOE4 status were found. Meanwhile, we did not find a nonlinear relationship between nocturnal sleep duration and CSF PGRN. Sleep problems may influence the metabolism of PGRN, thus attenuating the protective effects of PGRN on neurodegeneration diseases.

4.
Environ Toxicol Pharmacol ; 81: 103545, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33171223

RESUMO

As an important environmental pollutant, the heavy metal cadmium has a significant negative impact on the stability of the ecological environment and on organismal health. Previous studies have shown that cadmium chloride can damage the nervous, skeletal, endocrine, and reproductive systems, but to our knowledge, the effects of cadmium on the behavior, neurotransmitter levels, and neuronal development in the offspring of exposed animals have not been reported. In the present study, sexually-mature zebrafish were exposed to cadmium chloride at different concentrations for 60 days, and in this background, behavior, neurotransmitters level, neuro-development and neurotransmitter metabolism was investigated in the F1 offspring. The results showed that exposure of the parental zebrafish to cadmium chloride resulted swimming speed and distance of F1 offspring significantly reduced; the levels of neurotransmitters, such as dopamine, serotonin, and acetylcholine is disrupted. neuro-development and neurotransmitter metabolism related genes expression pattern was altered, which cause zebrafish F1 offspring developmental neurotoxicity. These findings provide further insights into the harm posed by cadmium chloride to the aquatic ecosystems.

5.
Scand J Gastroenterol ; 55(12): 1467-1474, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33169656

RESUMO

BACKGROUND: Esophageal bacteria, as the integral composition of human ecosystem, have been reported to be associated with esophageal lesions. However, few studies focus on microbial compositions in different esophageal segments, especially after Lugol's iodine staining (LIS) in the endoscopic examination for the screening of esophageal cancer. We aim to investigate the composition of the bacterial microbiome in upper, middle and lower esophagus and if LIS would affect the detection of bacteria. METHODS: A total of 141 fasting samples including the upper, middle and lower esophagus from 27 participants were collected by brushing the mucosal surface of the esophagus before (Eso) and after (Lug) LIS. Bacterial V3-V4 region of 16S rRNA gene was amplified and sequenced by Illumina's sequencing platform. RESULTS: The top six abundant bacterial phyla taxa among three locations from both Eso and Lug groups were Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and TM7. In terms of genera, the bacterium in three locations from two groups was all characterized by a highest relative abundance of Streptococcus. Bacteria diversity and the relative abundance between Eso and Lug were comparable (p > .05). Bacteria diversity was consistent in different esophageal locations within the individual. CONCLUSION: The bacterial microbiome in healthy esophagus are highly diverse and consistent even among three physiological sites at all clades. Lugol's iodine staining would not change local microenvironment in term of microbial composition. These findings provide an essential baseline for future studies investigating local and systemic bacterial microbiome and esophageal diseases.

6.
Sci Rep ; 10(1): 20324, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230189

RESUMO

Mitochondrial response to inflammation is crucial in the metabolic adaptation to infection. This study aimed to explore the mitochondrial response under inflammatory and anti-inflammatory environments, with a focus on the tricarboxylic acid (TCA) cycle. Expression levels of key TCA cycle enzymes and the autophagy-related protein light chain 3b (LC3b) were determined in raw 264.7 cells treated with lipopolysaccharide (LPS) and metformin (Met). Additionally, reactive oxygen species (ROS) levels and mitochondrial membrane potential were assessed using flow cytometry. Moreover, 8-week-old C57BL/6J mice were intraperitoneally injected with LPS and Met to assess the mitochondrial response in vivo. Upon LPS stimulation, the expression of key TCA enzymes, including citrate synthase, α-ketoglutarate dehydrogenase, and isocitrate dehydrogenase 2, and the mitochondrial membrane potential decreased, whereas the levels of LC3b and ROS increased. However, treatment with Met inhibited the reduction of LPS-induced enzyme levels as well as the elevation of LC3b and ROS levels. In conclusion, the mitochondrial TCA cycle is affected by the inflammatory environment, and the LPS-induced effects can be reversed by Met treatment.

7.
Carbohydr Res ; 498: 108195, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33220603

RESUMO

First observed in 1920s, the Warburg effects have inspired scientists to harness the unique glucose metabolism of cancer cells for targeted therapy for a century. Carbohydrate-drug conjugates are explicitly designed for selective uptake by cancer cells overexpressing glucose transporters. We summarize the progress in developing glycoconjugates for cancer-specific targeting and treatment over the past decade (2010-2020) and point to some future directions in this field.

8.
Biomater Sci ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201168

RESUMO

The whole is a collection of parts and fulfills specific functions that the parts do not have. In this work, 50 nm Au NPs were in situ synthesized and close packed into a superorganism-like superstructure by means of microgel 3D networks. The combined microgel is endowed with ultra-wide absorption in visible and near-infrared regions between 500 and 1100 nm in spite of Au NPs not having this property. The strong collective plasmon coupling between neighboring Au NPs induces high photothermal conversion efficiency of the microgel system under irradiation at various laser wavelengths. Due to the good loading capability, microgels with nanocomposites can also load photosensitive drugs simultaneously and be used for combined cancer treatments of photothermal therapy and photodynamic therapy.

9.
Chin J Nat Med ; 18(10): 721-722, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33039050
10.
Chin J Nat Med ; 18(10): 723-728, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33039051

RESUMO

D-Allose and its derivatives play important roles in the field of health care and food nutrition. Pure and well-defined D-allose derivatives can facilitate the elucidation of their structure-activity relationship as an essential step for drug design. The Lattrell-Dax epimerization, refers to the triflate inversion using nitrite reagent, is known as valuable method for the synthesis of rare D-allose derivatives. Here, the influence of protecting group patterns on the transformation efficiency of D-glucose derivatives into synthetically useful D-alloses and D-allosamines via the Lattrell-Dax epimerization was studied. For C3 epimerization of D-glucose derivatives bearing O2-acyl group, an anomeric configuration-dependent acyl migration from O2 to O3 was found. In addition, a neighbouring group participation effect-mediated SN1 nucleophilic substitution of the D-glucosamine bearing C2 trichloroacetamido (TCA) group in the Lattrell-Dax epimerization was dependent upon anomeric configuration. Thus, the effect of anomeric configuration on the Lattrell-Dax epimerization of D-glucose suggests that ß-D-glucosides with low steric hindrance at C2 should be better substrates for the synthesis of D-allose derivatives. Significantly, the efficient synthesis of the orthogonally protected D-allose 13 and D-allosamine 18 will serve well for further assembly of complex glycans.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33017482

RESUMO

Organic anodes have attracted increasing attention for alkali metal ion batteries. In this work, we discovered that cyclized polyacrylonitrile (cPAN) can serve as an excellent anode for alkali metal ion batteries. Upon activation cycling, as an anode of lithium-ion battery, cPAN exhibits a reversible capacity as high as 1238 mAh g-1 under a current density of 50 mA g-1 . Based on electrochemical experiments and first-principles calculations, it is demonstrated that the hexagonal carbon ring, piperidine ring, and pyridine nitrogen in ladder cPAN are the main active sites for lithium-ion storage. cPAN displays a unique potential-dependent solid electrolyte interphase formation from 0.1 to 0.01 V vs. Li/Li+ . It also displays decent performance as an anode in SIBs and PIBs.

12.
Blood ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33080623

RESUMO

This Phase 2 study evaluated isatuximab as monotherapy or combined with dexamethasone in relapsed/refractory multiple myeloma (RRMM). Patients had RRMM refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI) or had received ≥3 prior lines of therapy incorporating an IMiD and PI. Patients received isatuximab either as monotherapy (20 mg/kg on days 1, 8, 15, and 22 [once weekly] of cycle 1 followed by 20 mg/kg on days 1 and 15 of subsequent cycles; Isa group) or in combination with dexamethasone (40 mg/day [20 mg/day in patients ≥75 years] once weekly; Isa-dex group). Treated patients (N = 164) had received a median of 4 (range, 2-10) prior treatment lines. Patients received a median of 5 (1-24) and 7 (1-22) treatment cycles; at data cut-off, 13/109 (11.9%) and 15/55 (27.3%) patients remained on treatment in the Isa and Isa-dex arms, respectively. Overall response rate (primary efficacy endpoint) was 23.9% in the Isa arm and 43.6% in the Isa-dex arm (odds ratio, 0.405; 95% confidence interval, 0.192-0.859, P = 0.008). Median progression-free survival and overall survival were 4.9 and 18.9 months for Isa, and 10.2 and 17.3 months for Isa-dex. Infusion reactions (mostly grade 1/2) and hematologic abnormalities were the most common adverse events. There was a similar incidence of grade ≥3 infections in both groups (22.0% and 21.8%). In conclusion, addition of dexamethasone to isatuximab increased response rates and survival outcomes with no detrimental effect on safety. This trial was registered at www.clinicaltrials.gov as NCT01084252.

13.
Cell Discov ; 6: 67, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083003

RESUMO

The translocase of the outer mitochondrial membrane (TOM) complex is the main entry gate for mitochondrial precursor proteins synthesized on cytosolic ribosomes. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the dimeric human TOM core complex (TOM-CC). Two Tom40 ß-barrel proteins, connected by two Tom22 receptor subunits and one phospholipid, form the protein-conducting channels. The small Tom proteins Tom5, Tom6, and Tom7 surround the channel and have notable configurations. The distinct electrostatic features of the complex, including the pronounced negative interior and the positive regions at the periphery and center of the dimer on the intermembrane space (IMS) side, provide insight into the preprotein translocation mechanism. Further, two dimeric TOM complexes may associate to form tetramer in the shape of a parallelogram, offering a potential explanation into the unusual structural features of Tom subunits and a new perspective of viewing the import of mitochondrial proteins.

14.
J Med Chem ; 63(21): 12595-12613, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33125843

RESUMO

Diabetes is characterized by pancreas dysfunction and is commonly associated with obesity. Hypoglycemic agents capable of improving ß-cell function and reducing body weight therefore are gaining increasing interest. Though glucagon-like peptide 1 receptor (GLP-1R)/cholecystokinin 2 receptor (CCK-2R) dual agonist ZP3022 potently increases ß-cell mass and improves glycemic control in diabetic db/db mice, the in vivo half-life (t1/2) is short, and its body weight reducing activity is limited. Here, we report the discovery of a series of novel GLP-1R/CCK-2R dual agonists. Starting from Xenopus GLP-1, dual cysteine mutation was conducted followed by covalent side chain stapling and albumin binder incorporation, resulting in a stabilized secondary structure, increased agonist potency, and improved stability. Further C-terminal conjugation of gastrin-6 generated GLP-1R/CCK-2R dual agonists, among which 6a and 6b showed higher stability and hypoglycemic activity than liraglutide and ZP3022. Desirably, 6a and 6b exhibited prominent metabolic benefits in diet-induced obesity mice without causing nausea responses and exerted considerable effects on ß-cell restoration in db/db mice. These preclinical studies suggest the potential role of GLP-1R/CCK-2R dual agonists as effective agents for treating diabetes and related metabolic disorders.


Assuntos
Peptídeo 1 Semelhante ao Glucagon/agonistas , Hipoglicemiantes/química , Receptor de Colecistocinina B/agonistas , Proteínas de Xenopus/agonistas , Xenopus laevis/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Teste de Tolerância a Glucose , Meia-Vida , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutagênese Sítio-Dirigida , Obesidade/metabolismo , Obesidade/patologia , Peptídeos/síntese química , Peptídeos/química , Peptídeos/metabolismo , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Receptor de Colecistocinina B/metabolismo , Relação Estrutura-Atividade , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo
15.
Asia Pac J Clin Oncol ; 16(6): 291-298, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32893999

RESUMO

Immune checkpoint inhibitors (ICIs) have made a breakthrough in cancer therapy. Patients treated with ICIs may develop immune-related adverse events (irAEs) due to the upregulated activity of the immune system. With the increasing use of ICIs, irAEs are more frequently reported and have become important challenges in many patients. Neurological irAEs, which include encephalitis, myelitis, aseptic meningitis, peripheral neuropathy, myasthenia gravis, and myositis, consist of a distinct group of neuroinflammatory disorders. These disorders are rare but frequently severe with high mortality and morbidity. Patients with neurological irAEs are generally responsive to immune-modulating therapy. Therefore, early recognition and treatment are the most important ways to improve their prognosis. Here, we provide a comprehensive review of neurological irAEs associated with ICIs and focus on these affecting central nervous systems.


Assuntos
/efeitos adversos , Doenças do Sistema Nervoso/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
16.
Health Qual Life Outcomes ; 18(1): 296, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883289

RESUMO

BACKGROUND: Myasthenia gravis (MG), a chronic neuromuscular disorder, can adversely affect patients' health-related quality of life (HRQoL), especially in women. The study aimed to evaluate the difference in HRQoL of women and men MG patients and explore the factors that mediate the relationship between gender and HRQoL. METHODS: A cross-sectional study was conducted among 1815 patients with MG in China. The revised 15-item MG quality of life scale (MG-QOL15r) was used to access patients' HRQoL in overall, physical, social and emotional domains. Socio-demographic information, diagnosis and treatment history, comorbidities, social support, active lifestyle and the MG activities of daily living scale (MG-ADL) were recorded and compared between women and men using the Student's t-test and Pearson's Chi-square test. Multivariable regression analyses were conducted to identify independent contributors to HRQoL, especially those affecting different gender. RESULTS: On average, female patients with MG reported a lower MG-QOL15r score than the males (44.49 ± 29.10 vs 49.32 ± 29.18). The association between gender and patients' HRQoL interacted with the number of comorbidities across the overall, physical and social domains of patients. As the number of comorbidities increased, the scores of HRQoL decreased and it was faster among females than the males (p < 0.05). Moreover, unemployment, exacerbation of the disease, and active lifestyle contributed to the patients' HRQoL across all domains. Unemployment (ß = - 4.99 [95%CI, - 7.80 to - 2.18], p < 0.001) and exacerbations (ß = - 8.49 [95%CI, - 11.43 to - 5.54], p < 0.001) were correlated with poorer HRQoL; while an active lifestyle had a positive impact on HRQoL (ß = 0.28 [95%CI, 0.16 to 0.40], p < 0.001). CONCLUSIONS: The results indicate that the HRQoL of women MG patients was lower than that of men. The relationship between gender and HRQoL is modulated by the number of comorbidities. Thus, to improve the HRQoL of women MG patients, symptomatic treatments might not be enough, their comorbid conditions should be considered as well. Additionally, employment status, MG exacerbations, and an active lifestyle have been found as determining factors of the patients' HRQoL, which suggests future interventions should cope with these factors to improve their quality of life.


Assuntos
Miastenia Gravis/psicologia , Qualidade de Vida , Atividades Cotidianas/psicologia , Adulto , China , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Inquéritos e Questionários
17.
Psychiatry Investig ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32933237

RESUMO

OBJECTIVE: Schizophrenia is one of the most devastating neuropsychiatric disorders. Genetic epidemiological studies have confirmed that schizophrenia is a genetic disease. Genes promoting neurodevelopment may be potential candidates for schizophrenia. As an adaptor linking a number of tyrosine kinase receptors in multiple intracellular signaling cascades, Src homology 2 domain containing transforming protein 3 (SHC3) is a member of the Shc-like adaptor protein family, and expressed predominantly in the mature neurons of the central nervous system (CNS). In the present study, we aimed to investigate the association of SHC3 and schizophrenia. METHODS: An independent case-control association study was performed in a sample including 710 schizophrenia patients and 1314 healthy controls from a Northeast Chinese Han population. RESULTS: The allelic and genotypic association analyses showed that four SNPs in SHC3 significantly associated with schizophrenia (rs2316280, rs4877041, rs944485 and rs7021743). The haplotype composing of these four SNPs also showed significantly individual and global association with schizophrenia. CONCLUSION: Our present results suggest SHC3 as a susceptibility gene for schizophrenia.

18.
Sci Total Environ ; 749: 141257, 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-32810707

RESUMO

Improving the management and protection of karst groundwater resources and addressing karst-related environmental and ecological problems still face challenges raised from the limited knowledge on the entire karstic Critical Zone (K-CZ), including soil, epikarst, the vadose and saturated zones. Particularly, there is still a lack of integrated understanding of K-CZ properties and major CZ processes across space and time. In this study, we measured and analyzed the hydrochemical and multiple stable isotopic compositions of soil water, surface- and groundwaters from various compartments of the K-CZ in a typical subtropical karst watershed - Qingmuguan (QKW), Southwestern China, in order to explore the source and spatiotemporal variations of water and solutes (C, N, S) within the K-CZ; thereby elucidating the hydrological and biogeochemical processes and their affecting factors. The results show that (i) the K-CZ of QKW is characterized by high heterogeneity and permeability, with fast and strong hydrologic variations in response to rainfall variability; (ii) water-CO2­carbonate interactions (i.e. carbonate weathering) are remarkably active in different zones and are significantly modulated by hydrologic dynamics and seasonal change in biological activities; (iii) efficient migration of nitrate and sulfate occurs across the surface toward the saturated aquifer zone, which is affected by the source availability, elemental transformation and flow transport processes; (iv) human activities have clearly influenced groundwater quality and the natural K-CZ processes, for example, exogenic acids of anthropogenic origin (e.g. acid precipitation and nitrogenous fertilizers from crop lands) have been proven to be involved in the carbonate weathering, with a contribution of ~20%-30%. Our study highlights the strong coupling of hydrological and various biogeochemical processes and the interactive connection among various layers of K-CZ. Thus, systematical monitoring along the CZ profile and a process-based dynamic approach to elucidating climatic and anthropogenic forcing are necessary to better understand the K-CZ properties and functions.

19.
J Chem Inf Model ; 60(12): 5794-5802, 2020 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-32786709

RESUMO

The ability of coronaviruses to infect humans is invariably associated with their binding strengths to human receptor proteins. Both SARS-CoV-2, initially named 2019-nCoV, and SARS-CoV were reported to utilize angiotensin-converting enzyme 2 (ACE2) as an entry receptor in human cells. To better understand the interplay between SARS-CoV-2 and ACE2, we performed computational alanine scanning mutagenesis on the "hotspot" residues at protein-protein interfaces using relative free energy calculations. Our data suggest that the mutations in SARS-CoV-2 lead to a greater binding affinity relative to SARS-CoV. In addition, our free energy calculations provide insight into the infectious ability of viruses on a physical basis and also provide useful information for the design of antiviral drugs.

20.
Chin J Nat Med ; 18(8): 628-632, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32768170

RESUMO

D-Glycero-D-mannno-heptose 1ß, 7-bisphosphate (HBPß) is an important intermediate for constructing the core structure of Gram-negative bacterial lipopolysaccharides and was reported as a pathogen-associated molecular pattern (PAMP) that regulates immune responses. HBPß with 3-O-amyl amine linker and its monophosphate derivative D-glycero-D-mannno-heptose 7-phosphate (HP) with 1α-amyl amine linker have been synthesized as candidates for immunity study of HBPß. The O3-amyl amine linker of heptose was installed by dibutyltin oxide-mediated regioselective alkylation under fine-tuned protecting condition. The stereoselective installation of 1ß-phosphate ester was achieved by NIS-mediated phosphorylation at low temperature. The strategy for installation of 3-O-amyl amine linker onto HBP derivative can be expanded to the syntheses of other conjugation-ready carbohydrates bearing anomeric phosphoester.

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