1.Chemical synthesis and antibody affinity of epitope fragments from Helicobacter pylori lipopolysaccharide
Hui ZHAO ; Xiaopeng ZOU ; Lei XIAO ; Jing HU ; Jian YIN
Journal of China Pharmaceutical University 2024;55(5):645-656
Helicobacter pylori(Hp)is responsible for chronic gastritis,peptic ulcers,and even gastric cancers.Currently,there is no vaccine to prevent or treat Hp infections.Here,we described the chemical synthesis of α-1,6-glucans with different lengths(di-to hexasaccharide),which are present in the core oligosaccharide of Hp lipopolysaccharide(LPS).The 1,2-cis-glucosidic bonds were constructed successfully using a synergistic glycosylation strategy based on acyl remote participation and solvent effects.The results of glycan microarrays indicated that all synthesized α-1,6-glucan fragments possessed a strong binding to IgG antibodies in both rabbit serum immunized with Hp O1 LPS and patient serum infected with Hp.The α-1,6-linked trisaccharide exhibited strong binding affinity to anti-LPS rabbit IgG antibodies.The α-1,6-glucan trisaccharide and pentasaccharide elicited a strong response to IgG antibodies in sera of most Hp-infected patients.Some patients'sera exhibited strong binding activity with α-1,6-linked disaccharide.The results suggest that the α-1,6-glucan disaccharide,trisaccharide and pentasaccharide could be important carbohydrate antigen fragments in Hp lipopolysaccharide.
2.Clinical Study on the Effect of Tongdu Tiaoshen Acupuncture on Cerebral Hemodynamics and Oxygen Free Radicals in Patients with Post-stroke Epilepsy
Jian-Shuang SHI ; Xiao-Yin WANG ; Min LI ; Mei-Luan SU ; Han-Hong ZOU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(9):2246-2253
Objective To explore the effect of Tongdu Tiaoshen acupuncture,a needling method for dredging governor vessel and regulating mind,on cerebral hemodynamics and oxygen free radicals in the patients with post-stroke epilepsy(PSE).Methods A total of 60 patients with PSE were randomly divided into a treatment group and a control group,with 30 cases in each group.Both groups were given basic treatment for lowering lipid level,controlling blood pressure and glucose contents,and counteracting platelet aggregation.Moreover,the control group was treated with Sodium Valproate Sustained-Release Tablets,and the treatment group was treated with Tongdu Tiaoshen acupuncture mainly on the acupoints of Baihui(GV20),Shenting(GV24),Shuigou(GV26),Fengfu(GV 16),Fengchi(GB20)based on the treatment for the control group.One month constituted a course of treatment,and the treatment for the two groups covered three courses of treatment.The number of epileptic seizures,the severity of electroencephalogram(EEG),the peak systolic velocity(Vs)and end diastolic velocity(Vd)of bilateral anterior cerebral arteries,middle cerebral arteries and posterior cerebral arteries detected by transcranial Doppler ultrasonography(TCD),and the changes in the peripheral levels of oxygen free radicals such as malondialdehyde(MDA),hydroxyl radical(OH),lipid peroxide(LPO)and superoxide dismutase(SOD)in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After three months of treatment,the total effective rate of the treatment group was 93.33%(28/30),and that of the control group was 73.33%(23/30).The intergroup comparison(tested by chi-square test)showed that the efficacy of the treatment group was significantly superior to that of the control group(P<0.05).(2)After treatment,the average monthly epileptic seizure frequency in the two groups was decreased when compared with that before treatment(P<0.05),and the decrease in the treatment group was more significant than that in the control group(P<0.05).(3)After treatment,the grading of EEG severity in the two groups was significantly improved when compared with that before treatment(P<0.05),and the improvement in the treatment group was significantly superior to that in the control group(P<0.05).(4)After treatment,the peripheral levels of oxygen free radicals of MDA,OH and LPO in the two groups were lower than those before treatment(P<0.05),and the peripheral level of SOD was higher than that before treatment(P<0.05).The decrease of MDA,OH and LPO levels and the increase of SOD level in the treatment group were significantly superior to those in the control group(P<0.05 or P<0.01).(5)After treatment,the values of cerebral hemodynamic indicators of Vs and Vd of both left and right anterior cerebral artery,middle cerebral artery and posterior cerebral artery in the two groups were higher than those before treatment(P<0.05),and the increase in the treatment group was significantly superior to that in the control group,the differences being statistically significant(P<0.05).(6)During the treatment,there were no fainting,sticking of needle,bleeding and rash occurring during acupuncture in the two groups,which indicated that the therapy had high safety.Conclusion Tongdu Tiaoshen acupuncture can significantly reduce the seizure frequency of PSE and improve the severity of epileptic EEG.Its therapeutic mechanism may be related with the decrease of the oxygen free radical levels and with the improvement of cerebral hemodynamics.
3.Analysis on the secondary attack rates of SARS-CoV-2 Omicron variant and the associated factors.
Qing Xiang SHANG ; Ke XU ; Qi Gang DAI ; Hao Di HUANG ; Jian Li HU ; Xin ZOU ; Li Ling CHEN ; Ye WEI ; Hai Peng LI ; Qian ZHEN ; Wei CAI ; Yin WANG ; Chang jun BAO
Chinese Journal of Preventive Medicine 2023;57(10):1550-1557
Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q1, Q3) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q1, Q3) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.
Humans
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Male
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Middle Aged
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Young Adult
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Adult
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COVID-19/epidemiology*
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Incidence
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SARS-CoV-2
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Logistic Models
4.Jiedu Huoxue Prescription Affects Plaque Stability in ApoE-/- Atherosclerosis Mice by Modulating PI3K/Akt/mTOR Signaling Pathway
Limei YIN ; Jian YUAN ; Kai CHEN ; Jie ZHANG ; Guangmei XIE ; Guohui ZOU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(12):112-120
ObjectiveTo investigate whether Jiedu Huoxue prescription can induce macrophage autophagy and inhibit inflammatory response to stabilize vulnerable plaques of atherosclerosis (AS) by regulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. MethodThirty ApoE-/- mice fed with high-fat diet were randomly assigned into model, low-, medium-, and high-dose (5.35, 10.7, and 21.4 g·kg-1·d-1, respectively) Jiedu Huoxue prescription (Chinese medicine), and rapamycin (2 mg·kg-1·d-1) groups. Six ApoE-/- mice fed with common diet were used as the control group, and 6 C57BL/6J mice fed with common diet as the blank group. The drugs or equal volume of normal saline were administrated by gavage after 7 weeks of modeling, and the treatment lasted for 4 weeks. The serum levels of lipids and inflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6)] were measured. Hematoxylin-eosin (HE) staining was employed to observe the pathological changes of the vascular wall of the aortic root. Immunohistochemistry was employed to detect the expression of macrophages/monocytes monoclonal antibody (MOMA-2) and α-smooth muscle actin (α-SMA). Transmission electron microscopy was employed to count the autophagosomes in the aorta, and Western blot to determine the protein levels of Beclin-1, LC3, PI3K, Akt, and mTOR. ResultCompared with the control group, the model group showed elevated serum levels of lipids, MCP-1, and IL-6 (P<0.05), inhibited expression of MOMA-2 and α-SMA (P<0.05, P<0.01), up-regulated protein level of Beclin-1 (P<0.05), and down-regulated protein levels of PI3K, Akt, and mTOR (P<0.05, P<0.01). The model group presented obvious atherosclerotic plaques on the inner wall of the aorta, infiltration of inflammatory cells in the plaque, thickened and disarranged vascular intima where the plaque was attached, decreased autophagosomes and mitochondria, and destroyed mitochondrial structure. Chinese medicine and rapamycin groups showed lower levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, MCP-1, and IL-6 (P<0.05), higher level of high-density lipoprotein cholesterol (P<0.05), inhibited expression of MOMA-2 and α-SMA (P<0.05, P<0.01), higher protein levels of Beclin-1 and LC3Ⅱ (P<0.05, P<0.01), and lower protein levels of PI3K, Akt, and mTOR (P<0.05, P<0.01) than the model group. Moreover, Chinese medicine and rapamycin groups showed only a small number of atherosclerotic plaques on the inner wall of the aorta, reduced infiltration of inflammatory cells and thickness of the blood vessel wall, and increased autophagosomes and autophagic lysosomes. ConclusionJiedu Huoxue prescription can improve lipid metabolism, enhance macrophage autophagy, and reduce AS-induced inflammation to improve the stability of vulnerable plaques in AS mice by inhibiting the PI3K/Akt/mTOR signaling pathway.
5.Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum.
Jia XUE ; Hai-Jie CHEN ; Yong-Yi ZHOU ; Jia-Huan YUAN ; Zhi-Chen CAI ; Nan WU ; Cui-Hua CHEN ; Xun-Hong LIU ; Li-Si ZOU ; Sheng-Xin YIN ; Wei YANG ; Jian-Ming CHENG
China Journal of Chinese Materia Medica 2023;48(13):3448-3461
A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.
Chromatography, High Pressure Liquid
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Epimedium
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Tandem Mass Spectrometry
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Chromatography, Liquid
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Multivariate Analysis
6.Analysis on the secondary attack rates of SARS-CoV-2 Omicron variant and the associated factors.
Qing Xiang SHANG ; Ke XU ; Qi Gang DAI ; Hao Di HUANG ; Jian Li HU ; Xin ZOU ; Li Ling CHEN ; Ye WEI ; Hai Peng LI ; Qian ZHEN ; Wei CAI ; Yin WANG ; Chang jun BAO
Chinese Journal of Preventive Medicine 2023;57(10):1550-1557
Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q1, Q3) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q1, Q3) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.
Humans
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Male
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Middle Aged
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Young Adult
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Adult
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COVID-19/epidemiology*
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Incidence
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SARS-CoV-2
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Logistic Models
7.Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study.
Wei SHEN ; Zhi ZHENG ; Xin-Zhu LIN ; Fan WU ; Qian-Xin TIAN ; Qi-Liang CUI ; Yuan YUAN ; Ling REN ; Jian MAO ; Bi-Zhen SHI ; Yu-Mei WANG ; Ling LIU ; Jing-Hui ZHANG ; Yan-Mei CHANG ; Xiao-Mei TONG ; Yan ZHU ; Rong ZHANG ; Xiu-Zhen YE ; Jing-Jing ZOU ; Huai-Yu LI ; Bao-Yin ZHAO ; Yin-Ping QIU ; Shu-Hua LIU ; Li MA ; Ying XU ; Rui CHENG ; Wen-Li ZHOU ; Hui WU ; Zhi-Yong LIU ; Dong-Mei CHEN ; Jin-Zhi GAO ; Jing LIU ; Ling CHEN ; Cong LI ; Chun-Yan YANG ; Ping XU ; Ya-Yu ZHANG ; Si-Le HU ; Hua MEI ; Zu-Ming YANG ; Zong-Tai FENG ; San-Nan WANG ; Er-Yan MENG ; Li-Hong SHANG ; Fa-Lin XU ; Shao-Ping OU ; Rong JU
Chinese Journal of Contemporary Pediatrics 2022;24(2):132-140
OBJECTIVES:
To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China.
METHODS:
A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined.
RESULTS:
The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05).
CONCLUSIONS
It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female
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Fetal Growth Retardation
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Gestational Age
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Hospitalization
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Humans
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Incidence
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Infant
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Infant, Newborn
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Infant, Premature
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Infant, Very Low Birth Weight
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Prospective Studies
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Risk Factors
8.Chemical synthesis of a synthetically useful L-galactosaminuronic acid building block.
Chun-Jun QIN ; Hong-Li HOU ; Mei-Ru DING ; Yi-Kuan QI ; Guang-Zong TIAN ; Xiao-Peng ZOU ; Jun-Jie FU ; Jing HU ; Jian YIN
Chinese Journal of Natural Medicines (English Ed.) 2022;20(5):387-392
Most bacterial cell surface glycans are structurally unique, and have been considered as ideal target molecules for the developments of detection and diagnosis techniques, as well as vaccines. Chemical synthesis has been a promising approach to prepare well-defined oligosaccharides, facilitating the structure-activity relationship exploration and biomedical applications of bacterial glycans. L-Galactosaminuronic acid is a rare sugar that has been only found in cell surface glycans of gram-negative bacteria. Here, an orthogonally protected L-galactosaminuronic acid building block was designed and chemically synthesized. A synthetic strategy based on glycal addition and TEMPO/BAIB-mediated C6 oxidation served well for the transformation of commercial L-galactose to the corresponding L-galactosaminuronic acid. Notably, the C6 oxidation of the allyl glycoside was more efficient than that of the selenoglycoside. In addition, a balance between the formation of allyl glycoside and the recovery of selenoglycoside was essential to improve efficiency of the NIS/TfOH-catalyzed allylation. This synthetically useful L-galactosaminuronic acid building block will provide a basis for the syntheses of complex bacterial glycans.
Carbohydrates
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Glycosides
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Oligosaccharides
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Oxidation-Reduction
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Polysaccharides/chemistry*
9.Expert consensus on rational usage of nebulization treatment on childhood respiratory system diseases.
Han Min LIU ; Zhou FU ; Xiao Bo ZHANG ; Hai Lin ZHANG ; Yi Xiao BAO ; Xing Dong WU ; Yun Xiao SHANG ; De Yu ZHAO ; Shun Ying ZHAO ; Jian Hua ZHANG ; Zhi Min CHEN ; En Mei LIU ; Li DENG ; Chuan He LIU ; Li XIANG ; Ling CAO ; Ying Xue ZOU ; Bao Ping XU ; Xiao Yan DONG ; Yong YIN ; Chuang Li HAO ; Jian Guo HONG
Chinese Journal of Pediatrics 2022;60(4):283-290
10.Chemical approaches towards installation of rare functional groups in bacterial surface glycans.
Chun-Jun QIN ; Mei-Ru DING ; Guang-Zong TIAN ; Xiao-Peng ZOU ; Jun-Jie FU ; Jing HU ; Jian YIN
Chinese Journal of Natural Medicines (English Ed.) 2022;20(6):401-420
Bacterial surface glycans perform a diverse and important set of biological roles, and have been widely used in the treatment of bacterial infectious diseases. The majority of bacterial surface glycans are decorated with diverse rare functional groups, including amido, acetamidino, carboxamido and pyruvate groups. These functional groups are thought to be important constituents for the biological activities of glycans. Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach. To date, a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans. This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans, and the chemical methods used for installation of these groups.
Bacterial Infections
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Humans
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Polysaccharides/chemistry*
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Structure-Activity Relationship

Result Analysis
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