基于修饰组和探针分子的重要途径代谢物筛选和注释新方法北大核心CSCD

植物次生代谢物在抵御生物/非生物胁迫、生物间互作以及信息传递等方面发挥重要作用,次生代谢途径解析对植物分子育种、天然产物合成等方面具有重要意义。液相色谱-高分辨串联质谱(LC-HRMS/MS)为次生代谢物鉴定及途径表征提供了技术手段。非靶向LC-HRMS/MS方法可获得丰富的质谱信号,包括一级质谱和二级质谱(MS,MS/MS),但受质谱数据库规模以及次生代谢物复杂性的制约,次生代谢物注释十分困难。该研究以玉米叶片中苯丙烷途径代谢物为例,发展用于非靶向代谢组数据中重要途径代谢物的高效筛选和注释新方法。首先,利用公共代谢途径数据库及文献获取参与苯丙烷代谢途径的61种修饰反应类型,进而从非靶向实验数据中筛选出修饰代谢组。其次,获取开源串联质谱数据中的苯丙烷类化合物作为探针分子,构建探针分子质谱数据库。将探针分子与修饰代谢组共建分子网络,锁定目标途径代谢物并注释结构。该方法在正、负离子模式下分别筛选出玉米叶片中392个和417个苯丙烷途径候选代谢物,去冗余后共注释出129个代谢物,涉及苯丙烷代谢的主要分支途径,如黄酮途径的8个类黄酮、19个氧苷类黄酮和32个碳苷类黄酮,31个羟基肉桂酸途径代谢物以及22个木脂素途径代谢物;其中26个在PubChem和SciFinder数据库中未见收录。该研究利用探针分子结合修饰组可快速锁定途径代谢物,且有助于快速、准确的网络传播注释,可显著提高目标途径代谢物筛选与注释效率,为植物次生代谢途径的深入解析提供分析手段。     

Electrochemical Detection of Tryptophan Metabolites via Kynurenine Pathway by Using Nanocarbon Films

We studied nanocarbon film electrodes with the aim of detecting tryptophan metabolites via the kynurenine pathway. The nanocarbon films were formed by using unbalanced magnetron sputtering, and they exhibited superior electrode properties including a wide potential window and a low background current as a result of the sp³-containing structure and ultraflat surface. These properties allowed us to detect certain tryptophan metabolites such as kynurenic acid (KYNA), which has a relatively high oxidation potential. We also investigated the effect of the sp²/sp³ ratio of the nanocarbon film as regards the electrode activity in relation to target molecules. We found that the sp²/sp³ ratio played important roles in both widening the potential window and obtaining superior electrode performance for the metabolites. The nanocarbon film with a high sp³ content was beneficial as regards the electrode performance with respect to the detection limit and sensitivity. Compared with conventional carbon-based electrodes, the nanocarbon film electrode with a high sp³ content exhibited higher electrode activity against KYNA while maintaining a low background current. Computational experiments revealed that the theoretical oxidation potential (E_ox) value for some targets coincided with that obtained in electrochemical experiments using our nanocarbon film electrode.     

Investigating the influence of pH,temperature and agitation speed on yellow pigment production by Penicillium aculeatum ATCC 10409

In this study, the combined effect of pH, temperature and agitation speed on yellow pigment production and mycelial growth of Penicillium aculeatum ATCC 10409 was investigated in whey media. Different pH levels (5, 6.5 and 8), temperatures (25, 30 and 35°C) and agitation speed levels (100 and 150 rpm) were tested to determine the best conditions to produce a fungal yellow pigment under submerged fermentation. The best production of yellow pigment (1.38 g/L) was obtained with a pH value of 6.5, a temperature of 30°C and an agitation speed of 150 rpm. In contrast, the maximal biomass concentration (11.12 g/L) was obtained at pH value of 8, a temperature of 30°C and an agitation speed of 100 rpm. These results demonstrated that biomass and yellow pigment production were not directly associated. The identification of the structure of unknown P. aculeatum yellow pigment was detected using UV absorption spectrum and FT-IR spectroscopy.     

New compound with DNA Topo I inhibitory activity purified from Penicillium oxalicum HSY05

Strain HSY05 was isolated from sea sediment collected from the South China Sea and was later identified as Penicillium oxalicum by 16S rDNA sequence analysis. Various chromatographic processes led to the isolation and purification of two metabolites from the fermentation culture of HSY05, including one new compound, 2,2′,4,4′-tetrahyoxy-8′-methyl-6-methoxy-acyl-ethyl-diphenylmethanone (1), and a known compound secalonic acid D (SAD, 2), as characterised by UV, IR, 1D, 2D-NMR and MS data. The inhibitory activities against topoisomerase I of these two compounds were evaluated. The result showed that in addition to the known topo I inhibitor SAD (2), compound 1 also exhibited a moderate inhibitory effect.     

Acrylamide‐functionalized graphene micro‐solid‐phase extraction coupled to high‐performance liquid chromatography for the online analysis of trace monoamine acidic metabolites in biological samples

Monoamine acidic metabolites in biological samples are essential biomarkers for the diagnosis of neurological disorders. In this work, acrylamide‐functionalized graphene adsorbent was successfully synthesized by a chemical functionalization method and was packed in a homemade polyether ether ketone micro column as a micro‐solid‐phase extraction unit. This micro‐solid‐phase extraction unit was directly coupled to high‐performance liquid chromatography to form an online system for the separation and analysis of three monoamine acidic metabolites including homovanillic acid, 5‐hydroxyindole‐3‐acetic acid, and 3,4‐dihydroxyphenylacetic acid in human urine and plasma. The online system showed high stability, permeability, and adsorption capacity toward target metabolites. The saturated extraction amount of this online system was 213.1, 107.0, and 153.4 ng for homovanillic acid, 5‐hydroxyindole‐3‐acetic acid, and 3,4‐dihydroxyphenylacetic acid, respectively. Excellent detection limits were achieved in the range of 0.08–0.25 μg/L with good linearity and reproducibility. It was interesting that three targets in urine and plasma could be actually quantified to be 0.94–3.93 μg/L in plasma and 7.15–19.38 μg/L in urine. Good recoveries were achieved as 84.8–101.4% for urine and 77.8–95.1% for plasma with the intra‐ and interday relative standard deviations less than 9.3 and 10.3%, respectively. This method shows great potential for online analysis of trace monoamine acidic metabolites in biological samples.     

Einige neue Ergebnisse über den chemischen Zustand von 99mTe-Radiopharmaka

Es wird zusammenfassend über systematische Untersuchungen zur Tc-Markierbarkeit pharmazeutisch interessanter Verbindungen berichtet. Anhand chemisch charakterisierter ⁹⁹Tc-Komplexe von Metaboliten des Citratcyclus, von Polyhydroxycerbindungen und von Mercaptoverbindungen werden strukturelle Anforderungen an wirksame Liganden für Technetium abgeleitet.     

Electrochemical Chlorination of Physcion – An Approach to Naturally Occurring Chlorinated Secondary Metabolites of Lichens

The electrochemical chlorination of physcion (=1,8‐dihydroxy‐3‐methoxy‐6‐methylanthracene‐9,10‐dione; 1 ) in AcOH and CH₂Cl₂ was investigated by cyclic voltammetry and prep.‐scale electrolysis. This approach provided access to a number of diverse biologically and pharmacologically interesting chlorinated secondary metabolites of lichen. Unlike the only previous literature report on the ‘classical’ chlorination of physcion ( 1 ), which allowed the preparation of 4‐chlorophyscion ( 2b ), 4,5‐dichlorophyscion ( 3b ), and 2,4,5‐trichlorophyscion ( 4 ), the present procedure also gave fragilin (=2‐chlorophyscion; 2a ) and 2,4‐dichlorophyscion ( 3a ), alongside the previously obtained 2b, 3b , and 4 . All of these compounds, except for 2a , were isolated by column chromatography and medium‐pressure liquid chromatography (MPLC) and characterized by spectral data. The preparative electrolysis with a 2 F?mol^?1 charge consumption in AcOH and 10 F?mol^?1 in CH₂Cl₂ may have a practical synthetic utility, since the thus obtained product mixtures can be readily fractioned by column chromatography to afford pure 2b and 4 , respectively. The regioselectivity of the reaction is explained by the resonance stabilization of the corresponding arenium cations ‐ potential products of an electrophilic attack of a ‘positive’ Cl species on the physcion molecule.     

Synthesis and antitumor activity of puupehedione and related compounds

The first enantiospecific synthesis of bioactive marine puupehedione (2) and related compounds from (−)-sclareol (11) is reported. The antitumor activity of these compounds was assayed and compared with that of the natural products.     

Synthesis of Metabolites and Related Substances of Rabeprazole,an Anti-Ulcerative Drug

Rabeprazole sodium (Aciphex®) is a gastric proton pump inhibitor used for the prevention and treatment of gastric acid–related diseases. During the synthesis of bulk drug of rabeprazole sodium, we have observed metabolites rabeprazole sulfide and rabeprazole sulfone and related substances rabeprazole-N-oxide, rabeprazole sulfone-N-oxide, N-aralkyl rabeprazole, chloro rabeprazole, and methoxy rabeprazole as impurities in the drug substance. The present work describes the synthesis and characterization of these compounds.