Ubiquitin(Ub) chain isopeptide bond mimics are useful molecules for biochemical and biophysical studies. Herein, we report the semi-synthesis of the disulfide-linked K11/K48-branched tri-Ub(Ub_3^(11/48)(S-S)), the fir...Ubiquitin(Ub) chain isopeptide bond mimics are useful molecules for biochemical and biophysical studies. Herein, we report the semi-synthesis of the disulfide-linked K11/K48-branched tri-Ub(Ub_3^(11/48)(S-S)), the first example of an isopeptide mimic for the branched Ub chains,which have recently emerged as an interesting category of Ub modifications. Our strategy comprised the El-dependent synthesis of the Ub conjugate of aminoethanethiol, followed by disulfide formation with Ub(K11 C, K48 C). The structure of the synthetic isopeptide bond mimics was verified by the crystal structure of Ub_3^(11/48)(S-S). Deubiquitination and pulldown assays indicated that the synthetic Ub_3^(11/48)(S-S) could be hydrolyzed by linkage-specific deubiquitinases(K11-specific Cezanne and K48-specific OTUB1), and recognized by proteasomal ubiquitin receptor S5 a.展开更多
The Diels–Alder(D–A)reaction is one of the most powerful reactions in organic synthesis.The intermolecular D–A reaction attracts much less attentions than its intramolecular counterpart in natural product synthesis...The Diels–Alder(D–A)reaction is one of the most powerful reactions in organic synthesis.The intermolecular D–A reaction attracts much less attentions than its intramolecular counterpart in natural product synthesis,possibly due to the issues of reactivity and selectivity.In the past decade,the intermolecular D–A reaction has been increasingly utilized in the total synthesis of structurally complex natural products.In this article,we present a few examples for the elegant applications of the intermolecular D–A reaction that are inspired by biosynthetic hypotheses of the target natural products.These examples demonstrate that D–A reaction is not only useful for preparing building blocks but also powerful for coupling structurally complicated and sterically demanding segments in a highly chemo-and stereo-controlled fashion,which may inspire further developments of intermolecular D–A reaction from both strategy and methodology perspectives.展开更多
基金supported by the National Key R&D Program of China(2017YFA0505200)the National Natural Science Foundation of China(91753205,21532004,21761142008)the Program of Introducing Talents of Discipline to Universities of China(B16028)
文摘Ubiquitin(Ub) chain isopeptide bond mimics are useful molecules for biochemical and biophysical studies. Herein, we report the semi-synthesis of the disulfide-linked K11/K48-branched tri-Ub(Ub_3^(11/48)(S-S)), the first example of an isopeptide mimic for the branched Ub chains,which have recently emerged as an interesting category of Ub modifications. Our strategy comprised the El-dependent synthesis of the Ub conjugate of aminoethanethiol, followed by disulfide formation with Ub(K11 C, K48 C). The structure of the synthetic isopeptide bond mimics was verified by the crystal structure of Ub_3^(11/48)(S-S). Deubiquitination and pulldown assays indicated that the synthetic Ub_3^(11/48)(S-S) could be hydrolyzed by linkage-specific deubiquitinases(K11-specific Cezanne and K48-specific OTUB1), and recognized by proteasomal ubiquitin receptor S5 a.
基金financially supported by the Ministry of Science&Technology(2013CB836900)the National Natural Science Foundation of China(21290180,21172235,and 21222202)the Chinese Academy of Sciences
文摘The Diels–Alder(D–A)reaction is one of the most powerful reactions in organic synthesis.The intermolecular D–A reaction attracts much less attentions than its intramolecular counterpart in natural product synthesis,possibly due to the issues of reactivity and selectivity.In the past decade,the intermolecular D–A reaction has been increasingly utilized in the total synthesis of structurally complex natural products.In this article,we present a few examples for the elegant applications of the intermolecular D–A reaction that are inspired by biosynthetic hypotheses of the target natural products.These examples demonstrate that D–A reaction is not only useful for preparing building blocks but also powerful for coupling structurally complicated and sterically demanding segments in a highly chemo-and stereo-controlled fashion,which may inspire further developments of intermolecular D–A reaction from both strategy and methodology perspectives.
