HIV- 1 RT is an important target for the treatment of AIDS. There are two major classes of antiviral agents that inhibit HIV- 1 RT have been identified, nucleoside RT inhibitors （NRTIs） and non-nucleoside RT inhibit...HIV- 1 RT is an important target for the treatment of AIDS. There are two major classes of antiviral agents that inhibit HIV- 1 RT have been identified, nucleoside RT inhibitors （NRTIs） and non-nucleoside RT inhibitors （NNRTIs）. In this report, a noval class of non-nucleoside compound with potential RT inhibitory activity were found from the traditional Chinese medicines database （TCMD） using a combination of virtual screening, docking, molecular dynamic simulations, where results were ranked by scoring function of the docking tool. The result indicates that M4753 （a compound derived from TCMD） has not only the lowest bonding energy but also the best match in geometric conformation with the forthcoming NNRTIs. Accordingly M4753 might possibly become a promising lead compound of NNRTIs for AIDS therapy.展开更多
To apply an individualized oncological approach to gastric cancer patients,the accurate diagnosis of disease entities is required.Peritoneal metastasis is the most frequent mode of metastasis in gastric cancer,and the...To apply an individualized oncological approach to gastric cancer patients,the accurate diagnosis of disease entities is required.Peritoneal metastasis is the most frequent mode of metastasis in gastric cancer,and the tumor-node-metastasis classification includes cytological detection of intraperitoneal cancer cells as part of the staging process,denoting metastatic disease.The accuracy of cytological diagnosis leaves room for improvement;therefore,highly sensitive molecular diagnostics,such as an enzyme immunoassay,reverse transcription polymerase chain reaction,and virusguided imaging,have been developed to detect minute cancer cells in the peritoneal cavity.Molecular targeting therapy has also been spun off from basic research in the past decade.Although conventional cytologyis still the mainstay,novel approaches could serve as practical complementary diagnostics to cytology in near future.展开更多
HIV-1 reverse transcriptase（RT） inhibitors are major components of HAART（highly active antiviral therapy）. The S-DABOs（dihydro-alkylthio-benzyl-oxopyrimidines） series and their similar skeletons have exhibited p...HIV-1 reverse transcriptase（RT） inhibitors are major components of HAART（highly active antiviral therapy）. The S-DABOs（dihydro-alkylthio-benzyl-oxopyrimidines） series and their similar skeletons have exhibited preferable activities to inhibit HIV-1 RT. In the present study, we generated field-based QSAR models using common structure alignment, which was characterized by Gaussian steric, electrostatic, hydrophobic, hydrogen bond donor, hydrogen bond acceptor and aromatic ring fields（R2 = 0.8421, RCV2 = 0.5949 for the training set, Q2 = 0.5486, Pearson-r = 0.7460 for the test set）. Docking, pocket surface and contour map analyses were carried out. Key pharmacophore features were investigated, including（i） π-π interaction with residue Tyr181, Tyr188 and Trp229, σ-π interaction with His236,（ii） hydrogen bond with residue Lys101 and halogen bond with residue Tyr188. The docking analysis and field-based QSAR models could provide reasonable guidance in the rational design of potent HIV-1 RT inhibitors.展开更多
Objective： To summary the recent advances in molecular research of glioblastoma （GBM） and current trends in personalized therapy of this disease.Data Sources： Data cited in this review were obtained mainly from Pu...Objective： To summary the recent advances in molecular research of glioblastoma （GBM） and current trends in personalized therapy of this disease.Data Sources： Data cited in this review were obtained mainly from PubMed in English up to 2015, with keywords ＆quot;molecular＆quot;, ＆quot;genetics＆quot;, ＆quot;GBM＆quot;, ＆quot;isocitrate dehydrogenase＆quot;, ＆quot;telomerase reverse transcriptase＆quot;, ＆quot;epidermal growth factor receptor＆quot;, ＆quot;PTPRZ1-MET＆quot;, and ＆quot;clinical treatment＆quot;.Study Selection： Articles regarding the morphological pathology of GBM, the epidemiology of GBM, genetic alteration of GBM, and the development of treatment for GBM patients were identified, retrieved, and reviewed.Results： There is a large amount of data supporting the view that these recurrent genetic aberrations occur in a specific context of cellular origin, co-oncogenic hits and are present in distinct patient populations.Primary and secondary GBMs are distinct disease entities that affect different age groups of patients and develop through distinct genetic aberrations.These differences are important, especially because they may affect sensitivity to radio-and chemo-therapy and should thus be considered in the identification of targets for novel therapeutic approaches.Conclusion： This review highlights the molecular and genetic alterations of GBM, indicating that they are of potential value in the diagnosis and treatment for patients with GBM.展开更多
Studies of protein-ligand interactions are helpful to elucidating the mechanisms of ligands, providing clues for rational drug design. The currently developed steered molecular dy- namics (SMD) is a complementary appr...Studies of protein-ligand interactions are helpful to elucidating the mechanisms of ligands, providing clues for rational drug design. The currently developed steered molecular dy- namics (SMD) is a complementary approach to experimental techniques in investigating the biochemical processes occurring at microsecond or second time scale, thus SMD may provide dynamical and kinetic processes of ligand-receptor binding and unbinding, which cannot be ac- cessed by the experimental methods. In this article, the methodology of SMD is described, and the applications of SMD simulations for obtaining dynamic insights into protein-ligand interactions are illustrated through two of our own examples. One is associated with the simulations of bind- ing and unbinding processes between huperzine A and acetylcholinesterase, and the other is concerned with the unbinding process of α-APAfrom HIV-1 reverse transcriptase.展开更多
Among the structurally diverse NNRTIs, pyridinone scaffolds demonstrate high potency against HIV-1 wild type and drug-resistant strains. During the optimization of our pyridinone compound 1（LAM-trans）, we found that...Among the structurally diverse NNRTIs, pyridinone scaffolds demonstrate high potency against HIV-1 wild type and drug-resistant strains. During the optimization of our pyridinone compound 1（LAM-trans）, we found that the introduction of the N atoms in the C-4 position could dramatically improve the water solubility（7b）, whereas protonation of the piperidine N atom resulted in a decrease in its hydrophobic interaction with the binding pocket. In particular, protonation altered the orientation of the alicyclic rings in the hydrophobic pocket, thus impeding the formation of key halogen bond and eventually leading to a huge change in anti-HIV-1 RT activity. These results provided theoretical and experimental basis for the subsequent structural modification of pyridinone compounds.展开更多
目的克隆一个新的人睾丸特异性基因。方法运用电子差异展示方法筛选人类睾丸特异表达新基因,获得有差异显示的代表新基因的克隆重叠群,挑选其中一个克隆重叠群Hs.180197进行多组织RT-PCR验证该重叠群在人睾丸中的表达。然后从包含该重...目的克隆一个新的人睾丸特异性基因。方法运用电子差异展示方法筛选人类睾丸特异表达新基因,获得有差异显示的代表新基因的克隆重叠群,挑选其中一个克隆重叠群Hs.180197进行多组织RT-PCR验证该重叠群在人睾丸中的表达。然后从包含该重叠群的IMAGE克隆出发,采用生物信息学方法克隆一个人类新基因的全长cDNA序列。结果新基因全长1197bp,开放阅读框为504～806bp,定位于6p21.1-p21.2,编码由100个氨基酸组成,相对分子质量为10000,等电点为6.81的一个蛋白,该蛋白与已知蛋白无同源性。克隆实验验证该基因阅读框完全正确,推测其可能与精子生成相关,暂命名为TDRG1(testis development related gene1),GenBank登录号为DQ168992。结论电子差异展示方法与实验验证相结合用于发现人类功能新基因是行之有效的。展开更多
基金supported by the grants from Chinese National Science Foundation(No.30472166)the Tianjin Commission of Sciences and Technology under the Contract(No.06YFGZSH07000)
文摘HIV- 1 RT is an important target for the treatment of AIDS. There are two major classes of antiviral agents that inhibit HIV- 1 RT have been identified, nucleoside RT inhibitors （NRTIs） and non-nucleoside RT inhibitors （NNRTIs）. In this report, a noval class of non-nucleoside compound with potential RT inhibitory activity were found from the traditional Chinese medicines database （TCMD） using a combination of virtual screening, docking, molecular dynamic simulations, where results were ranked by scoring function of the docking tool. The result indicates that M4753 （a compound derived from TCMD） has not only the lowest bonding energy but also the best match in geometric conformation with the forthcoming NNRTIs. Accordingly M4753 might possibly become a promising lead compound of NNRTIs for AIDS therapy.
基金Supported by Grants from Ministry of Education,Science,and Culture,Japan(to Kagawa S)and JSPS KAKENHI,No.23591932
文摘To apply an individualized oncological approach to gastric cancer patients,the accurate diagnosis of disease entities is required.Peritoneal metastasis is the most frequent mode of metastasis in gastric cancer,and the tumor-node-metastasis classification includes cytological detection of intraperitoneal cancer cells as part of the staging process,denoting metastatic disease.The accuracy of cytological diagnosis leaves room for improvement;therefore,highly sensitive molecular diagnostics,such as an enzyme immunoassay,reverse transcription polymerase chain reaction,and virusguided imaging,have been developed to detect minute cancer cells in the peritoneal cavity.Molecular targeting therapy has also been spun off from basic research in the past decade.Although conventional cytologyis still the mainstay,novel approaches could serve as practical complementary diagnostics to cytology in near future.
基金National Natural Science Foundation of China(Grant No.21172014,20972011,21042009,21272017 and 81172917)Grants from the Ministry of Science and Technology of China(Grant No.2009ZX09301-010)
文摘HIV-1 reverse transcriptase（RT） inhibitors are major components of HAART（highly active antiviral therapy）. The S-DABOs（dihydro-alkylthio-benzyl-oxopyrimidines） series and their similar skeletons have exhibited preferable activities to inhibit HIV-1 RT. In the present study, we generated field-based QSAR models using common structure alignment, which was characterized by Gaussian steric, electrostatic, hydrophobic, hydrogen bond donor, hydrogen bond acceptor and aromatic ring fields（R2 = 0.8421, RCV2 = 0.5949 for the training set, Q2 = 0.5486, Pearson-r = 0.7460 for the test set）. Docking, pocket surface and contour map analyses were carried out. Key pharmacophore features were investigated, including（i） π-π interaction with residue Tyr181, Tyr188 and Trp229, σ-π interaction with His236,（ii） hydrogen bond with residue Lys101 and halogen bond with residue Tyr188. The docking analysis and field-based QSAR models could provide reasonable guidance in the rational design of potent HIV-1 RT inhibitors.
文摘Objective： To summary the recent advances in molecular research of glioblastoma （GBM） and current trends in personalized therapy of this disease.Data Sources： Data cited in this review were obtained mainly from PubMed in English up to 2015, with keywords ＆quot;molecular＆quot;, ＆quot;genetics＆quot;, ＆quot;GBM＆quot;, ＆quot;isocitrate dehydrogenase＆quot;, ＆quot;telomerase reverse transcriptase＆quot;, ＆quot;epidermal growth factor receptor＆quot;, ＆quot;PTPRZ1-MET＆quot;, and ＆quot;clinical treatment＆quot;.Study Selection： Articles regarding the morphological pathology of GBM, the epidemiology of GBM, genetic alteration of GBM, and the development of treatment for GBM patients were identified, retrieved, and reviewed.Results： There is a large amount of data supporting the view that these recurrent genetic aberrations occur in a specific context of cellular origin, co-oncogenic hits and are present in distinct patient populations.Primary and secondary GBMs are distinct disease entities that affect different age groups of patients and develop through distinct genetic aberrations.These differences are important, especially because they may affect sensitivity to radio-and chemo-therapy and should thus be considered in the identification of targets for novel therapeutic approaches.Conclusion： This review highlights the molecular and genetic alterations of GBM, indicating that they are of potential value in the diagnosis and treatment for patients with GBM.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.20102007,29725203 and 20072042)the State Key Program of Basic Research of China(Grant No.2002CB512802)+1 种基金the 863 Hi-Tech Program of China(Grant Nos.2002AA233011,2002AA233061,2001AA235051 and 2001AA 235041)Foundation of Shanghai Ministry of Science and Technology,and the Key Program of New Drug Research and Development from the Chinese Academy of Sciences.
文摘Studies of protein-ligand interactions are helpful to elucidating the mechanisms of ligands, providing clues for rational drug design. The currently developed steered molecular dy- namics (SMD) is a complementary approach to experimental techniques in investigating the biochemical processes occurring at microsecond or second time scale, thus SMD may provide dynamical and kinetic processes of ligand-receptor binding and unbinding, which cannot be ac- cessed by the experimental methods. In this article, the methodology of SMD is described, and the applications of SMD simulations for obtaining dynamic insights into protein-ligand interactions are illustrated through two of our own examples. One is associated with the simulations of bind- ing and unbinding processes between huperzine A and acetylcholinesterase, and the other is concerned with the unbinding process of α-APAfrom HIV-1 reverse transcriptase.
基金The National Natural Science Foundation of China(Grant No.21172014,20972011 and 21042009)
文摘Among the structurally diverse NNRTIs, pyridinone scaffolds demonstrate high potency against HIV-1 wild type and drug-resistant strains. During the optimization of our pyridinone compound 1（LAM-trans）, we found that the introduction of the N atoms in the C-4 position could dramatically improve the water solubility（7b）, whereas protonation of the piperidine N atom resulted in a decrease in its hydrophobic interaction with the binding pocket. In particular, protonation altered the orientation of the alicyclic rings in the hydrophobic pocket, thus impeding the formation of key halogen bond and eventually leading to a huge change in anti-HIV-1 RT activity. These results provided theoretical and experimental basis for the subsequent structural modification of pyridinone compounds.
文摘目的克隆一个新的人睾丸特异性基因。方法运用电子差异展示方法筛选人类睾丸特异表达新基因,获得有差异显示的代表新基因的克隆重叠群,挑选其中一个克隆重叠群Hs.180197进行多组织RT-PCR验证该重叠群在人睾丸中的表达。然后从包含该重叠群的IMAGE克隆出发,采用生物信息学方法克隆一个人类新基因的全长cDNA序列。结果新基因全长1197bp,开放阅读框为504～806bp,定位于6p21.1-p21.2,编码由100个氨基酸组成,相对分子质量为10000,等电点为6.81的一个蛋白,该蛋白与已知蛋白无同源性。克隆实验验证该基因阅读框完全正确,推测其可能与精子生成相关,暂命名为TDRG1(testis development related gene1),GenBank登录号为DQ168992。结论电子差异展示方法与实验验证相结合用于发现人类功能新基因是行之有效的。
