As an alternative method, matrix-assisted laser desorption/ionization with Fourier transform mass spectrometry （MALDI-FTMS） has been successfully used to detect and identify free radical adducts with small molecular...As an alternative method, matrix-assisted laser desorption/ionization with Fourier transform mass spectrometry （MALDI-FTMS） has been successfully used to detect and identify free radical adducts with small molecular weights of hydroxyl and 2-cyano-2-propyl radicals trapped with 5,5-dimethylpyrroline N-oxide （DMPO）. The detection and identification by MS/MS experiments using sustained offresonance irradiation collision-induced dissociation （SORI-CID） of [（DMPO＋·OH-·H）＋H^＋] （m/z 130.0868） and [DMPO＋2 ·CH（CH3）2CN＋H^＋] （m/z 250.1917） have demonstrated that MALDI-FTMS could be an effective method for detection and identification of free radical adducts. Other radical adducts have been also detected and identified. The approach of MALDI-FTMS is simple, fast, and sensitive which has potential for high-throughput analysis.展开更多
Molecular self-assembly is very ordinary phenomenon in the biological process such as protein folding,DNA encoding and etc.Inspired by this inherent biological process,nanostructure such as nanofibers,nanosphere,and s...Molecular self-assembly is very ordinary phenomenon in the biological process such as protein folding,DNA encoding and etc.Inspired by this inherent biological process,nanostructure such as nanofibers,nanosphere,and so on formed by the therapeutic agents and its derivatives that can further self-assemble into supramolecular hydrogels have attained considerable attentions in the field of drug delivery due to its favorable features such as high and precise drug payload,carrier-free and excellent biocompatibility.Additionally,the prodrug hydrogelator can be rationally designed to fine-tune over its drug release behavior and degradation in response to various biological stimulus（temperature,p H,ionic strength and etc.）.This review summarized and discussed the recent advancement in the self-assembled small molecular weight hydrogels of prodrugs.展开更多
AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by compu...AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors. Cytotoxic effect of syl-155 on three tumor cell lines with various states of p53, HT1080 (wild-type p53), KYSE510 (mutant p53), MG63 (p53 deficiency) was evaluated by MTT assay, Western blot and flow cytometry.RESULTS: Syl-155 stimulated the accumulation of p53 and p21 protein in HT1080 cells expressing wild-type p53, but not in KYSE510 and MG63 cells. Consequently, syl-155 induced cell cycle arrest and apoptosis in HT1080 cells.CONCLUSION: Non-peptidic small molecular inhibitors of the p53-HDM2 interaction show promise in treatment of tumors expressing wild-type p53.展开更多
基金Project supported by the National Natural Science Foundation of China （Nos. 20475063 and 20475059） and Chinese Academy of Sciences （No. KGCX2-SW-213-04）.
文摘As an alternative method, matrix-assisted laser desorption/ionization with Fourier transform mass spectrometry （MALDI-FTMS） has been successfully used to detect and identify free radical adducts with small molecular weights of hydroxyl and 2-cyano-2-propyl radicals trapped with 5,5-dimethylpyrroline N-oxide （DMPO）. The detection and identification by MS/MS experiments using sustained offresonance irradiation collision-induced dissociation （SORI-CID） of [（DMPO＋·OH-·H）＋H^＋] （m/z 130.0868） and [DMPO＋2 ·CH（CH3）2CN＋H^＋] （m/z 250.1917） have demonstrated that MALDI-FTMS could be an effective method for detection and identification of free radical adducts. Other radical adducts have been also detected and identified. The approach of MALDI-FTMS is simple, fast, and sensitive which has potential for high-throughput analysis.
基金financially supported by grants from the National Natural Science Foundation of China(No.31671022)the Key Program for International S&T Cooperation Projects of China(No.2015DFA50310)the National Science and Technology Major Project(No.2014ZX09303301)
文摘Molecular self-assembly is very ordinary phenomenon in the biological process such as protein folding,DNA encoding and etc.Inspired by this inherent biological process,nanostructure such as nanofibers,nanosphere,and so on formed by the therapeutic agents and its derivatives that can further self-assemble into supramolecular hydrogels have attained considerable attentions in the field of drug delivery due to its favorable features such as high and precise drug payload,carrier-free and excellent biocompatibility.Additionally,the prodrug hydrogelator can be rationally designed to fine-tune over its drug release behavior and degradation in response to various biological stimulus（temperature,p H,ionic strength and etc.）.This review summarized and discussed the recent advancement in the self-assembled small molecular weight hydrogels of prodrugs.
基金Supported by the China Key Program on Basic Research,G1998051102 and G1998051021 National Science Foundation of China, 39870862
文摘AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors. Cytotoxic effect of syl-155 on three tumor cell lines with various states of p53, HT1080 (wild-type p53), KYSE510 (mutant p53), MG63 (p53 deficiency) was evaluated by MTT assay, Western blot and flow cytometry.RESULTS: Syl-155 stimulated the accumulation of p53 and p21 protein in HT1080 cells expressing wild-type p53, but not in KYSE510 and MG63 cells. Consequently, syl-155 induced cell cycle arrest and apoptosis in HT1080 cells.CONCLUSION: Non-peptidic small molecular inhibitors of the p53-HDM2 interaction show promise in treatment of tumors expressing wild-type p53.
文摘目的高通量筛选技术筛选抑制肝癌(PLC)细胞生长的新型小分子化合物。方法将PLC HepG2、Huh7细胞进行培养,培养后用于实验。选择3个小分子化合物数据库(合计3272个小分子化合物),分别为Prestwick、Tocriscreen、Selleck Chem。以及进行高通量筛选和靶化合物的筛选。结果本研究从3272个小分子化合物中利用高通量筛选技术选出抑制PLC细胞生长的目的化合物(hits)。初筛出的hits为z-score<-1.5,差异有统计学意义( P <0.05)。本研究通过比较9块化合物筛选板2种PLC细胞系(HepG2、Huh7)的重叠区域,共筛选出31种能够同时抑制这2个细胞系生长,且z-score<-1.5的化合物。最终筛选出36种hits化合物,包括5种临床治疗PLC的常用化疗药物和分子式。阿霉素作为hits被2次筛选出来,故最终初筛成功的新型化合物共有31种。结论通过高通量筛选技术筛选出31种可能具有抑制PLC细胞生长作用的新型小分子化合物,且有可能成为PLC治疗中的新型靶向药物。
