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11.
磺酰脲类除草剂的三维药效团模型 总被引:3,自引:0,他引:3
磺酰脲类除草剂是七十年代末期[1,2]开发的一类超高效除草剂,杀草谱广,用量极低.它通过抑制植物体内乙酰乳酸合成酶(ALS,acetolactatesynthase)的活性[3],破坏支链氨基酸缬氨酸、亮氨酸和异亮氨酸的合成,造成杂草的死亡.本文从三维角度出发,利用先进的三维分子设计软件APEX(ActivityPredictionExpertSystem)-3D[4],建立破酸豚类除草剂药效团模型(biophoremodel),辅助设计、筛选活性化合物;再由药效团构造出模拟ALS酶活性位点(activesites)的空间结构,以该模拟结构为基点,以期设计出全新结构的ALS酶抑制剂的… 相似文献
12.
在AHAS与磺酰脲类除草剂复合物的晶体结构基础上, 利用分子对接程序DOCK 4.0, 通过MDL/ACD三维数据库虚拟筛选, 得到了296个与AHAS结合能较低的小分子化合物结构信息, 从中选取了部分小分子进行化学合成, 并且测试了其生物活性. 部分化合物的体内和体外活性表现出一定的一致性. 相似文献
13.
《Angewandte Chemie (International ed. in English)》2017,56(4):1146-1151
8‐demethyl‐8‐aminoriboflavin‐5′‐phosphate (AFP) synthase (RosB) catalyzes the key reaction of roseoflavin biosynthesis by forming AFP from riboflavin‐5′‐phosphate (RP) and glutamate via the intermediates 8‐demethyl‐8‐formylriboflavin‐5′‐phosphate (OHC‐RP) and 8‐demethyl‐8‐carboxylriboflavin‐5′‐phosphate (HO2C‐RP). To understand this reaction in which a methyl substituent of an aromatic ring is replaced by an amine we structurally characterized RosB in complex with OHC‐RP (2.0 Å) and AFP (1.7 Å). RosB is composed of four flavodoxin‐like subunits which have been upgraded with specific extensions and a unique C‐terminal arm. It appears that RosB has evolved from an electron‐ or hydride‐transferring flavoprotein to a sophisticated multi‐step enzyme which uses RP as a substrate (and not as a cofactor). Structure‐based active site analysis was complemented by mutational and isotope‐based mass‐spectrometric data to propose an enzymatic mechanism on an atomic basis. 相似文献
14.
After the cultured cells from Hyoscyamus muticus + Nicotiana tabacum somatic hybridswere cocultivated with different virulent strains of Agrobacterium tumefaciens harboringoctopine- type Ti plasmid or nopaline- type Ti plasmid using the transformation procedurein vitro developed in the present investigation, the TiT- DNA genes were introducedinto the host cells. The onc genes and ocs or nos genes located on TiT- DNA were expres-sed in transformed colonies derived from the cocultivated cells. Although the platingefficiencies of recipient cells were reduced by the agrobacterial treatment, the frequenciesof phytohormone autotrophy ranged from 33.9 to 76 .8% in the cells infected with viru-lent strains in hormone- free conditions, and the frequencies of opine synthase activityamounted to 9.7- 47 .5%. Teratomatous shoots were regenerated from the transformed col-onies. During the course of culture the shoots were no longer to lengthen when theygrew up to 1 -3 cm in length, and they could not be rooted. Follo 相似文献
15.
Yang Y Nie W Yuan J Zhang B Wang Z Wu Z Guo Y 《Experimental & molecular medicine》2010,42(11):768-776
Deregulation of endothelial nitric oxide synthase (eNOS) plays an important role in the development of multiple cardiovascular diseases. Our recent study demonstrated that genistein supplementation attenuates pulmonary arterial hypertension in broilers by restoration of endothelial function. In this study, we investigated the molecular mechanism by using broiler pulmonary arterial endothelial cells (PAECs). Our results showed that genistein stimulated a rapid phosphorylation of eNOS at Ser(1179) which was associated with activation of eNOS/NO axis. Further study indicated that the activation of eNOS was not mediated through estrogen receptors or tyrosine kinase inhibition, but via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent signaling pathway, as the eNOS activity and related NO release were largely abolished by pharmacological inhibitors of PI3K or Akt. Thus, our findings revealed a critical function of Akt in mediating genistein-stimulated eNOS activity in PAECs, partially accounting for the beneficial effects of genistein on the development of cardiovascular diseases observed in animal models. 相似文献
16.
Inrecentyears,agrowingnumberofscientistsareIookingforpr0cedurestolabelbiologicallyimp0rtantmolecules(suchasDNA,Proteins,etc.)'-'.Oneefficientwaycurrentlyexploitedistheuseofnear-infraredfluorescentdyesasfluorogeniclabels.AIthoughtherearemanyfluorescentdyescommerciallyavailable,onlyseveralclassesofm0lecuIescanbe0peratedinthefar-visibleornear-infraredregion(6O0-lO00nm)whicharetheareas0flowinterference.Inanattemptt0lookfornewnear-infraredfluorescentmolecules,0urgroupsynthesizedaseriesofbenzo[a… 相似文献
17.
Dr. Yongjun Zhou Prof. Patrícia Prediger Prof. Luiz Carlos Dias Dr. Annabel C. Murphy Prof. Peter F. Leadlay 《Angewandte Chemie (International ed. in English)》2015,54(17):5232-5235
Elaiophylin is an unusual C2‐symmetric antibiotic macrodiolide produced on a bacterial modular polyketide synthase assembly line. To probe the mechanism and selectivity of diolide formation, we sought to reconstitute ring formation in vitro by using a non‐natural substrate. Incubation of recombinant elaiophylin thioesterase/cyclase with a synthetic pentaketide analogue of the presumed monomeric polyketide precursor of elaiophylin, specifically its N‐acetylcysteamine thioester, produced a novel 16‐membered C2‐symmetric macrodiolide. A linear dimeric thioester is an intermediate in ring formation, which indicates iterative use of the thioesterase active site in ligation and subsequent cyclization. Furthermore, the elaiophylin thioesterase acts on a mixture of pentaketide and tetraketide thioesters to give both the symmetric decaketide diolide and the novel asymmetric hybrid nonaketide diolide. Such thioesterases have potential as tools for the in vitro construction of novel diolides. 相似文献
18.
Dr. Yuriy Rebets Dr. Elke Brötz Niko Manderscheid Dr. Bogdan Tokovenko Dr. Maksym Myronovskyi Prof. Dr. Peter Metz Dr. Lutz Petzke Dr. Andriy Luzhetskyy 《Angewandte Chemie (International ed. in English)》2015,54(7):2280-2284
Pamamycins are macrodiolides of polyketide origin with antibacterial activities. Their biosynthesis has been proposed to utilize succinate as a building block. However, the mechanism of succinate incorporation into a polyketide was unclear. Here, we report identification of a pamamycin biosynthesis gene cluster by aligning genomes of two pamamycin‐producing strains. This unique cluster contains polyketide synthase (PKS) genes encoding seven discrete ketosynthase (KS) enzymes and one acyl‐carrier protein (ACP)‐encoding gene. A cosmid containing the entire set of genes required for pamamycin biosynthesis was successfully expressed in a heterologous host. Genetic and biochemical studies allowed complete delineation of pamamycin biosynthesis. The pathway proceeds through 3‐oxoadipyl‐CoA, a key intermediate in the primary metabolism of the degradation of aromatic compounds. 3‐Oxoadipyl‐CoA could be used as an extender unit in polyketide assembly to facilitate the incorporation of succinate. 相似文献
19.
Application of chromatography technology in the separation of active alkaloids from Hypecoum leptocarpum and their inhibitory effect on fatty acid synthase 下载免费PDF全文
Qiulong Zhang Guangxiang Luan Tao Ma Na Hu Yourui Suo Xiaoyan Wang Xiaofeng Ma Chenxu Ding 《Journal of separation science》2015,38(23):4063-4070
A method that involved the combination of pH‐zone‐refining counter‐current chromatography and semipreparative reversed‐phase liquid chromatography has been established for the preparative separation of alkaloids from Hypecoum leptocarpum. From 1.2 g of crude sample, 31 mg N‐feruloyltyramine, 27 mg oxohydrastinine, 47 mg hydroprotopine, 25 mg leptopidine, and 18 mg hypecocarpine have been obtained. The structure of the new compound, hypecocarpine, is confirmed based on the analysis of spectroscopic data, including NMR, UV, and IR spectroscopy and positive electrospray ionization mass spectrometry. The known chemical structures were characterized on the basis of 1H and 13C NMR spectroscopy. The purities of the five alkaloids are all over 92.7% as determined by high‐performance liquid chromatography. The alkaloids’ cytotoxicity in breast cancer cells is assessed by using a Cell Counting Kit assay and their inhibitory effect on fatty acid synthase expression is assessed by a Western blot assay. These results suggest that leptopidine could suppress growth and induce cytotoxicity in breast cancer cells and that the cytotoxicity of leptopidine may be related to its inhibitory effect on fatty acid synthase expression. 相似文献
20.
Qi Chen Ji-Wei Zhang Lu-Lu Chen Jun Yang Xin-Ling Yang Yun Ling Qing Yang 《中国化学快报》2017,28(6):1232-1237
Chitin is a structural component of fungal cell walls but is absent in vertebrates,mammals,and humans.Chitin synthase is thus an attractive molecular target for developing fungicides.Based on the structure of its donor substrate,UDP-N-acetyl-glucosamine,as well as the modelled structure of the bacterial chitin synthase NodC,we designed a novel scaffold which was then further optimized into a series of chitin synthase inhibitors.The most potent inhibitor,compound 13,exhibited high chitin synthase inhibitory activity with an IC_(50) value of 64.5 μmol/L All of the inhibitors exhibited antifungal activities against the growth of agriculturally-destructive fungi,Fusarium graminearum,Botrytis cinerea.and Colletotrichum lagenarium.This work presents a new scaffold which can be used for the development of novel fungicides. 相似文献