Protein amyloid aggregate:Structure and function

Protein amyloid aggregation has been widely observed to occur and plays impor-tant roles in both physiological processes and pathological diseases.Remarkably,amyloid aggregates assembled by native proteins gain a variety of different biolog-ical activities,which cannot be adopted by the unassembled protein alone.Thus,it is important to investigate the molecular basis of self-assembly of protein amyloid aggregates and how the aggregated protein structure determines its function.In the review,wefirstly introduce our structural knowledge on how different amyloid pro-teins undergo conformational transition and assemble into amyloid aggregate,with the main focus on amyloidfibril,which is the major species of amyloid aggregate.Then,we elaborate how different structures of amyloidfibrils enable them to fulfill highly diverse functions in either physiological or pathological condition.Further-more,we discuss the structural polymorph which is a very unique feature of amyloidfibril,and its implication in understanding the structure-function relationship of amy-loidfibrils.Finally,we point out the importance of applying and integrating new approaches for deepening the structure-function study of amyloidfibrils and high-light the potential of designing amyloidfibril-based functional bio-nanomaterials for application.

Studies on the Physicochemical Properties, Structure and Antitumor Activity of Polysaccharide YhPS-1 from the Root of Cordalis yanhusuo Wang

多糖说出 YhPS-1 从 Cordalis yanhusuo 王的根被孤立并且借助于胶化浸透净化了层析和 ionexchange 层析。包括 monosaccharide 作文，糖类内容，分子的重量和元素的作文，它的物理化学的性质是坚定的。YhPS-1 的结构被化学方法与 1H 和 13C NMR 光谱学方法一起阐明，例如包括二维的 HMQC 和 HMBC 实验。这些结果证明 YhPS-1 拥有由终端 -Glcp-(1,-Glcp-(16),-Glcp-(14) 和 -Glcp-(14,6) 组成的一根脊梁。bioactive 试金证明它能禁止肉瘤 180 的生长和肺的癌在老鼠植入的路易斯。

Mining of a streptothricin gene cluster from Streptomyces sp.TP-A0356 genome via heterologous expression

Streptothricins (STs) are used commercially to treat bacterial and fungal diseases in agriculture. Mining of the sequenced microbial genomes uncovered two cryptic ST clusters from Streptomyces sp. C and Streptomyces sp. TP-A0356. The ST cluster from S. sp. TP-A0356 was verified by successful heterologous expression in Streptomyces coelicolor M145. Two new ST analogs were produced together with streptothricin F and streptothricin D in the heterologous host. The ST cluster was further confirmed by inactivation of gene stnO, which was proposed encoding an aminomutase supplying -lysines for the poly-β-Lys chain formation. A putative biosynthetic pathway for STs is proposed based on bioinformatics analyses of the ST genes and experimental evidence.

The PHD1 finger of KDM5B recognizes unmodified H3K4 during the demethylation of histone H3K4me2/3 by KDM5B

KDM5B 是 histone H3K4me2/3 demethylase。KDM5B 的 PHD1 领域为 demethylation 是批评的，但是位于这个领域的行动下面的机制是不清楚的。在这份报纸，我们观察了那 PHD1 < 潜水艇 class= “ a-plus-plus ” > KDM5B 与 unmethylated H3K4me0 交往。我们 PHD1 的 NMR 结构 < 潜水艇 class= “ a-plus-plus ” > 在有 H3K4me0 的建筑群的 KDM5B 表明有约束力的模式与另外的报导哲学博士手指的稍微不同。由在接口(L325A/D328A ) 的残余上的两倍变化的这个相互作用的混乱减少在在约 50% 的房间和增加的 KDM5B 的 H3K4me2/3 demethylation 活动肿瘤 suppressor 基因由的 transcriptional 压抑近似双重。这些调查结果暗示那 PHD1 < 潜水艇 class= “ a-plus-plus ” > KDM5B 可以帮助在目标基因维持 KDM5B 调停 KDM5B 的 demethylation 活动。

Synthesis of C-Aryl-flavonoid Derivatives via Suzuki-Miyaura Coupling Reaction

许多 4-C-aryl-quercetin 和 3-C-aryl-quercetin 衍生物方便地经由与芳基 boronic 酸或 boronates 相应 quercetin-O-triflates 联合的 Suzuki-Miyaura 被综合。

Synthesis of the ABC skeleton of the aglycon of Echinoside A

Echinoside A is a triterpene saponin isolated from the sea cucumber Actinopyga echinites(JAEGER), which displays potent antitumor activities in vitro and in vivo. Here, we report the synthesis of the ABC-fused ring skeleton of the aglycon of Echinoside A, with the enantiomerically pure(+)-Wieland–Miescher ketone being used as starting material and a Robinson annulation as the key reaction.

Emerging roles of podoplanin in vascular development and homeostasis

Podoplanin (PDPN ) 是在多样的房间类型表示的粘蛋白类型 O-glycoprotein，例如在脉管的系统和 fibroblastic 的淋巴的 endothelial 房间(LEC ) 在淋巴节点的网状的房间(FRC ) 。LEC 或 FRC 上的 PDPN 在血小板激活 CLEC-2，触发通过下游地表明事件的血小板激活或聚集，包括 Syk kinase 的激活。这机制被要求开始并且维持血和淋巴管的分离并且在淋巴节点以内稳定高 endothelial 小静脉正直。在脉管的系统，在 LEC 表面的 PDPN 的正常表示与核心 1-derived O-glycans 由 PDPN 的 Prox1 和修正要求 Pdpn 的 transcriptional 激活。这评论在脉管的开发和淋巴的机关维护提供 PDPN 的角色的全面概述并且讨论调整与它的函数有关的 PDPN 表示的机制。

Carbohydrate-based drugs launched during 2000-2021

Carbohydrates are fundamental molecules involved in nearly all aspects of lives,such as being involved in formating the genetic and energy materials,supporting the structure of organisms,constituting invasion and host defense systems,and forming antibiotics secondary metabolites.The naturally occurring carbohydrates and their derivatives have been extensively studied as therapeutic agents for the treatment of various diseases.During 2000 to 2021,totally 54 carbohydrate-based drugs which contain carbohydrate moities as the major structural units have been approved as drugs or diagnostic agents.Here we provide a comprehensive review on the chemical structures,activities,and clinical trial results of these carbohydrate-based drugs,which are categorized by their indications into antiviral drugs,antibacterial/antiparasitic drugs,anticancer drugs,antidiabetics drugs,cardiovascular drugs,nervous system drugs,and other agents.

Ligand-free nickel-catalyzed Kumada couplings of aryl, bromides with tert-butyl Grignard reagents

A ligand-free nickel-catalyzed Kumada cross-coupling of aryl bromides and tert-butyl Grignard reagents led to the formation of a series of tert-butyl aryls in moderate to good yields, excellent tBu/iBu ratios, and good functional group compatibility. A radical coupling process is indicated and a mechanism with a Ni(Ⅰ)-Ni(Ⅲ) catalytic cycle is proposed.

Synthesis and Insecticidal Structure-Activity Relationships of Novel Tonghaosu Analogs

21 tonghaosu 类似物经由 hydroamination 或 endocyclic 的选择减小被综合相应 dienol spiroketals 的两倍契约。所有新混合物的结构被 1H NMR，红外， MS， HREIMS 或元素的分析证实。他们对大白蝴蝶(Pieris brassicae L ) 的 antifeedant 活动和向蚊子的 larvicidal 活动(一种蚊虫 quinquefasciatus 说) 被检验。他们中的一些展出了比得上或比 tonghaosu Z-1 强壮的 antifeeding 活动。基于活动数据，初步的结构活动关系也被讨论，它可能为以后与更好的 bioactivities 发现铅混合物是有启发性的。

In vivo investigation of the role of SfmO2 in saframycin A biosynthesis by structural characterization of the analogue saframycin O

Saframycin A(SFM-A),a tetrahydroisoquinoline antibiotic isolated from Streptomyces lavendulae,shows potent anti-proliferation activities against a variety of tumor cell lines,and shares the core structure with ecteinascidin 743(ET-743),the anticancer drug for soft-tissue sarcoma.Characterization of the SFM-A biosynthetic gene cluster revealed three nonribosomal peptide synthetase genes and a series of genes encoding oxygenases.To investigate the function of sfmO2 gene,encoding a FAD-dependent monooxygenase/hydroxylase,we constructed the gene replacement mutant(△sfmO2) strain S.lavendulae TL2007 and the corresponding gene complementation mutant strain S.lavendulae TL2008.A novel compound,SFM-O,was isolated from the △sfmO2 replacement mutant strain and its structure was characterized by comparison to the HRMS and NMR spectra of SFM-A.These findings indicated that SfmO2 is responsible for the oxidation of ring A in the biosynthetic pathway of SFM-A,and the new compound SFM-O could be considered as an advanced intermediate in the semisynthesis of ET-743.

Synthesis of a 1,2,7,8-Tetraoxa-spiro[5.5]undecane

新 spiro 的合成器官的过氧化物被描述。peroxy 契约作为 peroxy 连接的来源用氢过氧化物经由催化酸的 ketal 交换反应被合并到底层框架。hydroperoxyl 组然后经由导致的 Hg (II ) 在 OH 结束被结合 C-C 的 electrophilic 增加加倍契约，在每二枚六成员的戒指与一张 peroxy 契约给新奇 sprio 结构。在方面链的酉旨功能也使进行进一步结构的修正可能。

Synthesis of 5,6-Dihydro-OSW-1 and Its Antitumor Activities

5,6-Dihydro-OSW-1 (1) was synthesized following our previous procedure for the total synthesis of OSW-1. This compound demonstrated slightly stronger potency than that of OSW-1 against the growth of cancer cells.

Deciphering the Origin and Formation of Aminopyrrole Moiety in Kosinostatin Biosynthesis

Kosinostatin(KST)contains an uncommon aminopyrrole moiety,whose biosynthesis has remained elusive.Herein,aminopyrrolinic acid,which was generated by an L-ectoine synthase-like enzyme KstB3 via cyclization of L-glutamine,was identified to be the real substrate of adenylation enzyme KstB1.Subsequently,a FAD-dependent dehydrogenase KstB4 along with a transglutaminase-like enzyme KstB6 were also involved in formation of aminopyrrole.These results provided an unusual pathway for 2-aminopyrrole formation in KST biosynthesis.

Ethacrynic acid targets GSTM1 to ameliorate obesity by promoting browning of white adipocytes

Dear Editor,Obesity is caused by an imbalance between energy intake and expenditure,and has become a global epidemic with over 650 million adults affected.Adipose tissues in mammals are composed of white adipose tissue(WAT)and classical brown adipose tissue(BAT),and their balance is highly related to the occurrence of obesity.The browning of white adipocytes results in“beige”or“brite”adipocytes,which appear functionally similar to classical brown adipocytes,and can be detected in WAT deposits of animals that have been exposed to cold or other inducers(Fu et al.,2015).

Synthesis and RNase A Substrate Properties of Conformationally Fixed U>P Derivatives

In enzyme-catalyzed reactions, there is not only a substrate-inducedconformational change in enzyme, but also an enzyme-induced conformational changein substrate.This "induced fit" serves to maximize the number and strength of theenzyme-substrate interaction. By means of nuclear magnetic resonance(NMR), usingcytidine 2′-, 3′- and 5′-monophosphate(2′-, 3′- and 5′-CMP) as inhibitors,Meadows et al. investigated the base orientation relative to the ribose moiety

Hydrogen bonded foldamer-bridged biscoumarins:A UV-Vis absorption and fluorescent study of the solvent effect

Three arylamide-bridged biscoumarin derivatives 1-3 have been designed and prepared. Compounds 1 and 2 are induced by the intramolecular N?H…O and N·H…F hydrogen bonding to possess a helical conformation,and 3 is induced to have an extended conformation. A comparison of their absorption and fluorescent spectra in a variety of solvents of a wide range of polarity with those of control compound 4 reveals that,for foldamers 1 and 2,the intramolecular hydrogen bonding and the helical conformations exist in most solvents,but do not exist or are very weak in DMF and DMSO.

11-Aza-artemisinin Derivatives Exhibit Anticancer Activities by Targeting the Fatty Acid Binding Protein 6(FABP6)

Artemisinin (Qinghaosu),a sesquiterpene lactone isolated from the Chinese medicinal herb Artemisia annua,is famous as the first-line antimalarial drug,and reported to also possess anticancer properties.Though many studies have proceeded focusing on artemisinin and bioactive deriva- tives in clinic or laboratory,their cellular targets and mechanism of actions have still remained obscure.Here,two new 11-aza-artemisinin derivatives AAD1and AAD2,which displayed cytotoxity against multiple cancer cell lines,were synthesized and applied as the probes for target identification and anticancer mechanism research.Using T7 phage display screen method,fatty acid binding protein 6(FABP6)was identified and verified as one of the potential targets.Further studies showed FABP6 is a direct binding protein of AAD1 and AAD2,and mediated the corresponding anticancer activities of these artemisinin derivatives.

Metalloporphyrin receptors for histidine-containing peptides

Two new ditopic metalloporphyrin receptors constructed by combining metalloporphyrin with crown ethers have been prepared and characterized.1H NMR and MS spectra confirmed the complexation of receptor with peptide driven by coordination interaction and hydrogen bonding.UV/vis experiments revealed that the receptors exhibited high binding affinity to histidine-containing peptides.These receptors could differentiate short peptides of C-terminal histidine and N-terminal histidine and formed the most stable complexes with tripeptide.