In this paper, we report a novel approach to the heteroaryl-condensed nuclei of natural furo[3,2- a]carbazole alkaloids. Our synthetic studies use N-phthaloyl tryptophan methyl ester as starting material and zinc ion ...In this paper, we report a novel approach to the heteroaryl-condensed nuclei of natural furo[3,2- a]carbazole alkaloids. Our synthetic studies use N-phthaloyl tryptophan methyl ester as starting material and zinc ion mediated transamination reaction as the key step. This work also implicated a novel strategy to assemble other [a]-fused carbazoles.展开更多
Seven photoaffinity-based and sixteen biotin-based berberine(BBR)probes were constructed and screened for their effects on c-Jun N-terminal protein kinases(JNK)phosphorylation(p-JNK)suppression at the cellular level.T...Seven photoaffinity-based and sixteen biotin-based berberine(BBR)probes were constructed and screened for their effects on c-Jun N-terminal protein kinases(JNK)phosphorylation(p-JNK)suppression at the cellular level.Taking active-photoaffinity probe 7c as a chemical tool,we first identified mitogen-activated protein kinase 7(MAP2K7),an upstream protein on the JNK/stress activated protein kinase(SAPK)pathway,as a direct proteomic target of BBR using activity-based protein profiling(ABPP)and other chemical proteomic techniques.Furthermore,BBR’s inhibitory effect on p-JNK was significantly attenuated in both the MAP2K7-knockdown and models,indicating a MAP2K7-dependent inhibition on the JNK signaling pathway.For the first time,we demonstrate the unique mechanism of BBR that directly targets MAP2K7 to inhibit p-JNK rather than JNK activity with the advantages of multiple activities and a good safety profile.展开更多
基金supported by NSFC (No.21102026)Qiankehe [2011] 3002West Light Foundation of the Chinese Academy of Sciences
文摘In this paper, we report a novel approach to the heteroaryl-condensed nuclei of natural furo[3,2- a]carbazole alkaloids. Our synthetic studies use N-phthaloyl tryptophan methyl ester as starting material and zinc ion mediated transamination reaction as the key step. This work also implicated a novel strategy to assemble other [a]-fused carbazoles.
基金supported by the CAMS Innovation Fund for Medical Sciences(nos.2020-I2M-2-010 and 2016-I2M-1-011)the Drug Innovation Major Project(no.2018ZX09711-001)the National Natural Science Foundation of China(no.81974494).
文摘Seven photoaffinity-based and sixteen biotin-based berberine(BBR)probes were constructed and screened for their effects on c-Jun N-terminal protein kinases(JNK)phosphorylation(p-JNK)suppression at the cellular level.Taking active-photoaffinity probe 7c as a chemical tool,we first identified mitogen-activated protein kinase 7(MAP2K7),an upstream protein on the JNK/stress activated protein kinase(SAPK)pathway,as a direct proteomic target of BBR using activity-based protein profiling(ABPP)and other chemical proteomic techniques.Furthermore,BBR’s inhibitory effect on p-JNK was significantly attenuated in both the MAP2K7-knockdown and models,indicating a MAP2K7-dependent inhibition on the JNK signaling pathway.For the first time,we demonstrate the unique mechanism of BBR that directly targets MAP2K7 to inhibit p-JNK rather than JNK activity with the advantages of multiple activities and a good safety profile.
