62096-93-9Relevant academic research and scientific papers
Cysteine-Activated Small-Molecule H2Se Donors Inspired by Synthetic H2S Donors
Cai, Xuekang,Cheng, Longhuai,Dong, Yalun,Huang, Haojie,Jiang, Chenyang,Kang, Xueying,Sang, Yueqian,Sun, Lu,Wen, Xin,Xi, Zhen,Yi, Long
, p. 3957 - 3967 (2022/03/08)
The importance of selenium (Se) in biology and health has become increasingly clear. Hydrogen selenide (H2Se), the biologically available and active form of Se, is suggested to be an emerging nitric oxide (NO)-like signaling molecule. Nevertheless, the research on H2Se chemical biology has technique difficulties due to the lack of well-characterized and controllable H2Se donors under physiological conditions, as well as a robust assay for direct H2Se quantification. Motivated by these needs, here, we demonstrate that selenocyclopropenones and selenoamides are tunable donor motifs that release H2Se upon reaction with cysteine (Cys) at pH 7.4 and that structural modifications enable the rate of Cys-mediated H2Se release to be tuned. We monitored the reaction pathways for the H2Se release and confirmed H2Se generation qualitatively using different methods. We further developed a quantitative assay for direct H2Se trapping and quantitation in an aqueous solution, which should also be operative for investigating future H2Se donor motifs. In addition, we demonstrate that arylselenoamide has the capability of Cys-mediated H2Se release in cellular environments. Importantly, mechanistic investigations and density functional theory (DFT) calculations illustrate the plausible pathways of Cys-activated H2Se release from arylselenoamides in detail, which may help understand the mechanistic issues of the H2S release from pharmacologically important arylthioamides. We anticipate that the well-defined chemistries of Cys-activated H2Se donor motifs will be useful for studying Se biology and for development of new H2Se donors and bioconjugate techniques.
Fast and Cysteine-Specific Modification of Peptides, Proteins and Bacteriophage Using Chlorooximes
Chen, Fa-Jie,Zheng, Mengmeng,Nobile, Vincent,Gao, Jianmin
supporting information, (2022/03/15)
This work reports a novel chlorooxime mediated modification of native peptides and proteins under physiologic conditions. This method features fast reaction kinetics (apparent k2=306±4 M?1s?1 for GSH) and exquisite selectivity for cysteine residues. This cysteine conjugation reaction can be carried out with just single-digit micromolar concentrations of the labeling reagent. The conjugates show high stability towards acid, base, and external thiol nucleophiles. A nitrile oxide species generated in situ is likely involved as the key intermediate. Furthermore, a bis-chlorooxime reagent is synthesized to enable facile Cys-Cys stapling in native peptides and proteins. This highly efficient cysteine conjugation and stapling was further implemented on bacteriophage to construct chemically modified phage libraries.
Metabolite profiling reveals a role for intercellular dihydrocamalexic acid in the response of mature Arabidopsis thaliana to Pseudomonas syringae
Kempthorne, Christine J.,Nielsen, Alexander J.,Wilson, Daniel C.,McNulty, James,Cameron, Robin K.,Liscombe, David K.
, (2021/04/12)
The leaf intercellular space is a site of plant-microbe interactions where pathogenic bacteria such as Pseudomonas syringae grow. In Arabidopsis thaliana, the biosynthesis of tryptophan-derived indolic metabolites is induced by P. syringae infection. Using high-resolution mass spectrometry-based profiling and biosynthetic mutants, we investigated the role of indolic compounds and other small molecules in the response of mature Arabidopsis to P. syringae. We observed dihydrocamalexic acid (DHCA), the precursor to the defense-related compound camalexin, accumulating in intercellular washing fluids (IWFs) without further conversion to camalexin. The indolic biosynthesis mutant cyp71a12/cyp71a13 was more susceptible to P. syringae compared to mature wild-type plants displaying age-related resistance (ARR). DHCA and structural analogs inhibit P. syringae growth (MIC ~ 500 μg/mL), but not at concentrations found in IWFs, and DHCA did not inhibit biofilm formation in vitro. However, infiltration of exogenous DHCA enhanced resistance in mature cyp71a12/cyp71a13. These results provide evidence that DHCA derived from CYP71A12 and CYP71A13 activity accumulates in the intercellular space and contributes to the resistance of mature Arabidopsis to P. syringae without directly inhibiting bacterial growth.
Synthesis, biological activities, and 3D-QSAR studies of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfonohydrazide moiety
Li, Fengyun,Li, Yuxin,Li, Zhengming,Liu, Jingbo,Wang, Yuanhong,Zhang, Haoxuan
, (2020/01/22)
To discover a novel lead structure for antiphytopathogenic fungus agent, a series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfonohydrazide moiety were designed and synthesized. They were determined by melting points, 1H NMR, 13C NMR, and elemental analysis (EA). The biological activity results revealed that these title compounds possessed antifungal and insecticidal activities. Some title compounds against Alternaria solani, Physalospora piricola, Cercospora arachidicola, Phytophthora capsici, Fusarium graminearum, and Sclerotinia sclerotiorum displayed moderate to good antifungal activities at 50 mg/L, especially, compounds 6b and 6p displayed good and broad-spectrum antifungal activities. The structure activity relationships were discussed. A 3D-QSAR model was established based on the antifungal activity against Phytophthora capsici, indicating that electrostatic and hydrophobic fields were the two most significant factors for antifungal activity. Hence, structure optimization based on the CoMSIA model was performed to find compound 6p with excellent activity against Phytophthora capsici, and the EC50 values of compound 6p were comparable to those of chlorothalonil. Furthermore, the insecticidal activity of compound 6p against Culex pipiens larvae at 1 mg/L was considerable to that of chlorantraniliprole. Therefore, compound 6p can be used as a novel lead structure for antiphytopathogenic fungus and insecticidal agent development.
Synthesis method of thiazoline heterocyclic compound and application of thiazoline heterocyclic compound in biomolecular modification
-
, (2020/01/12)
The invention discloses a synthesis method of a thiazoline heterocyclic compound and application of the thiazoline heterocyclic compound in biomolecular modification, and relates to the technical field of organic synthesis. The synthesis method comprises the following steps: mixing a thioalkene ether compound and a compound containing a 1, 2-mercaptoethylamine skeleton structure in a solvent, andadding a weak base to react for 60-240 minutes at the reaction temperature of 20-60 DEG C to obtain the dihydrothiazole heterocyclic compound. The synthesis method of the thiazolidine heterocyclic compound is mild and efficient, can quickly react in water at room temperature, and overcomes the defects of violent reaction conditions, long reaction time and the like in the traditional synthetic method; by means of the synthesis method, biomolecules such as polypeptide and protein containing the nitrogen-terminal cysteine residues can be efficiently and accurately modified, and application of detection and treatment methods and the like is further developed.
Condensation of 2-((Alkylthio)(aryl)methylene)malononitrile with 1,2-Aminothiol as a Novel Bioorthogonal Reaction for Site-Specific Protein Modification and Peptide Cyclization
Gao, Wei,Li, Xuefei,Li, Zhuoru,Luk, Louis Y. P.,Meng, Xiaoting,Tsai, Yu-Hsuan,Wu, Chuanliu,Zhao, Yibing,Zheng, Xiaoli
supporting information, (2020/03/16)
Site-specific modification of peptides and proteins has wide applications in probing and perturbing biological systems. Herein we report that 1,2-aminothiol can react rapidly, specifically and efficiently with 2-((alkylthio)(aryl)methylene)malononitrile (TAMM) under biocompatible conditions. This reaction undergoes a unique mechanism involving thiol-vinyl sulfide exchange, cyclization, and elimination of dicyanomethanide to form 2-aryl-4,5-dihydrothiazole (ADT) as a stable product. An 1,2-aminothiol functionality can be introduced into a peptide or a protein as an N-terminal cysteine or an unnatural amino acid. The bioorthogonality of this reaction was demonstrated by site-specific labeling of not only synthetic peptides and a purified recombinant protein but also proteins on mammalian cells and phages. Unlike other reagents in bioorthogonal reactions, the chemical and physical properties of TAMM can be easily tuned. TAMM can also be applied to generate phage-based ADT-cyclic peptide libraries without reducing phage infectivity. Using this approach, we identified ADT-cyclic peptides with high affinity to different protein targets, providing valuable tools for biological studies and potential therapeutics. Furthermore, the mild reaction conditions of TAMM condensation warrant its use with other bioorthogonal reactions to simultaneously achieve multiple site-specific modifications.
Synthesis, biological activities and 3D-QSAR studies of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfur ether moiety
Liu, Jingbo,Li, Fengyun,Wang, Yuanhong,Zhang, Haoxuan,Dong, Jingyue,Sun, Pengwei,Li, Yuxin,Li, Zhengming
supporting information, p. 668 - 671 (2018/11/27)
A series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfur ether moiety were synthesized and characterized on the basis of NMR and elemental analysis (EA). The crystal structure of (R)-N-(2-methyl-1-(methylthio)propan-2-yl)-2-(4-nitrophenyl)-4,5-dihydrothiazole-4-carboxamide (13d) was determined to show R configuration. The bioasssy results indicated that most title compounds displayed good and broad spectrum antifungal activities against several phytopathogenic fungi. The structure activity relationships were discussed. Based on the antifungal activity of title compounds against Phytophthora capsici, a CoMSIA calculation was performed to establish a 3D-QSAR model, which revealed that electrostatic and hydrophobic fields were the two most significant factors for antifungal activity. According to the established 3D-QSAR model, structure optimization was carried out to find (R)-N-((R)-1-(methylthio)propan-2-yl)-2-(p-tolyl)-4,5-dihydrothiazole-4-carboxamide (15h) with excellent activity against Phytophthora capsici, thus emerging as a new lead compound for novel antiphytopathogenic fungus agent development.
(R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a diacylhydrazine group: Synthesis, biological evaluation, and SARs
Li, Feng-Yun,Liu, Jing-Bo,Gong, Jia-Ning,Li, Gen
, (2019/12/26)
A series of (R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a diacylhydrazine moiety were designed and synthesized. Their structures were confirmed by melting points, 1H NMR, 13C NMR, and elemental analysis (EA). Their antifungal and insecticidal activities were evaluated. The antifungal activity result indicated that most title compounds against Cercospora arachidicola, Alternaria solani, Phytophthora capsici, and Physalospora piricola exhibited apparent antifungal activities at 50 mg/L, and better than chlorothalonil or carbendazim. The EC50 values of (R)-N'-benzoyl-2-(4-chlorophenyl)-4,5-dihydrothiazole-4-carbohydrazide (I-5) against six tested phytopathogenic fungi were comparable to those of chlorothalonil. The CoMSIA model showed that a proper hydrophilic group in the R1 position, as well as a proper hydrophilic and electron-donating group in the R2 position, could improve the antifungal activity against Physalospora piricola, which contributed to the further optimization of the structures. Meanwhile, most title compounds displayed good insecticidal activities, especially compound (R)-N'-(4-nitrobenzoyl)-2-(4-nitrophenyl)-4,5-dihydrothiazole-4-carbohydrazide (III-3). The insecticidal mechanism results indicated that compound III-3 can serve as e_ective insect Ca2+ level modulators by disrupting the cellular calcium homeostasis in Mythimna separata.
Cu(i)-Catalyzed oxidative homo-coupling of thiazoline-4-carboxylates: Synthesis of 4,4′-bithiazoline derivatives
Fang, Xinxin,Zhang, Kaifan,Yao, Hequan,Huang, Yue
supporting information, p. 8030 - 8034 (2016/09/09)
Cu(i)-Catalyzed oxidative homo-coupling of thiazoline-4-carboxylates with good functional group tolerance has been developed. The methodology presented an efficient method to directly construct vicinal carbon-hetero quaternary centers existing in numerous functional molecules and could be applied to the synthesis of 4,4′-bithiazoles which are difficult to prepare by direct C-H activation.
Ruthenium(II) complexes derived from 2-phenylthiazoline-4-carboxylic acid: Structure and catalytic activity for transfer hydrogenation reaction
Denizalt, Serpil,G?ke, Ayta Gürhan,en, Betül,etinkaya, Bekir
, p. 373 - 377 (2016/05/02)
Piano-stool ([(p-cymene)Ru(thz)Cl], 2) and six-coordinated ([Ru(thz)2(PPh3)2], 3) ruthenium complexes derived from 2-phenylthiazoline-4-carboxylic acid (Hthz, 1) were synthesized for the first time, and fully characterized using conventional methods. Also, the molecular structure of complex 3 was determined using X-ray analysis. These complexes were evaluated as catalysts for transfer hydrogenation of carbonyl compounds in the presence of isopropyl alcohol and KOtBu. Complex 2 was found to be more active than 3 in transfer hydrogenation.
