- Design, Synthesis, and Evaluation of Phospholipid Analogues as Inhibitors of the Bacterial Phospholipase C from Bacillus cereus
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Enzymes belonging to the phospholipase C (PLC) family hydrolyze the phosphodiester bond of phospholipids to give a diacylglycerol and a phosphorylated head group.The bacterial phospholipase C from Bacillus cereus (PLCBc) has been studied extensively, and there is a wealth of information regarding those structural features that are important for substrate activity.In contrast, there is virtually no data available regarding structure-activity relationships for inhibitors of this enzyme.To address this shortcoming, a series of optically pure analogues of 1,2-dihexanoyl-sn-glycero-3-phosphocholine (2) containing different replacements of the phosphate group were first synthesized including the phosphoramidates 4 and 8, the phosphonate 5, the (difluoromethylene)phosphonate 6, the thiophosphate 7, the diastereomeric phosphorothioates 9 and 10, and the phosphorodithioate 11.Each of these phosphatidylcholine derivatives was tested for inhibitor or substrate activity with PLCBc using the water-soluble phosphatidylcholine 2 as the monomeric substrate.The measurements were conducted below the critical micellar concentrations of both 2 and the inhibitor.Of the analogues, only 7 and 9 underwent observable enzymatic hydrolysis under the assay conditions used.The kcat of the (Sp)-phosphorothioate 9 was approximately one-fifth that of 2, and when compared to 2, 7 was hydrolyzed only very slowly by the enzyme.Kinetic studies indicated that the phospholipid analogues tested were competitive inhibitors with increasing Ki's as follows: 7 ca. 11 ca. 10 4 ca. 8 5 ca. 6.
- Martin, Stephen F.,Wong, Yue-Ling,Wagman, Allan S.
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- Bis-Acetyl Carbazole: A Photoremovable Protecting Group for Sequential Release of Two Different Functional Groups and Its Application in Therapeutic Release
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In this paper, we present fluorescent photoremovable protecting groups (FPRPG) based on bis-acetyl carbazole for the release of two different functional groups such as carboxylic acids, alcohols, thiols, and amines in a sequential fashion. Dual-arm caged bis-acetyl carbazoles with different combinations of two unlike functional groups were synthesized. Photophysical studies showed that caged bis-acetyl carbazoles are blue fluorescent and their emission properties are sensitive to the environment. Sequential photorelease of two different functional groups by bis-acetyl carbazole was analyzed by HPLC, UV and emission spectroscopy. The mechanism of the dual release by bis-acetyl carbazole was investigated and supported by TD-DFT calculations. To demonstrate the applicability of the dual release ability of bis-acetyl carbazole FPRPG, we synthesized a drug delivery system (DDS) in which one arm of bis-acetyl carbazole is linked to the carboxylic functional group of chlorambucil (CBL) and the other arm is attached to the hydroxyl group of ferulic acid ethyl ester (FAEE). In vitro studies showed that our DDS presents excellent properties such as photoregulated dual drug delivery, cellular uptake, and biocompatibility.
- Venkatesh, Yarra,Nandi, Surajit,Shee, Maniklal,Saha, Biswajit,Anoop, Anakuthil,Pradeep Singh
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- Toward the total synthesis of haliclonin a: Construction of a tricyclic substructure
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Three keys to success: A concise method for the construction of a tricyclic substructure (2) of haliclonin A (1) in racemic form is described (see figure). This synthesis features a new Pd-mediated chemoselective carbonyl-enone coupling reaction, an organ
- Luo, Shi-Peng,Guo, Lian-Dong,Gao, Long-Hui,Li, Shuang,Huang, Pei-Qiang
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supporting information
p. 87 - 91
(2013/02/25)
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- Catalyst-free, high-yield, and stereospecific synthesis of 3-phenylthio β-lactam derivatives
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α-Diazocarbonyl compounds are good precursors of ketenes in the Staudinger reaction. On the basis of the reactions of S-phenyl diazothioacetate with imines under the catalysis of Rh2(OAc)4 a method for the synthesis of 3-phenylthio β
- Jiao, Lei,Liang, Yong,Zhang, Qianfeng,Zhang, Shiwei,Xu, Jiaxi
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p. 659 - 665
(2007/10/03)
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- Heat-sensitive recording materials and phenol compounds
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Heat-sensitive recording materials contain an electron-donating chromogenic compound and an electron-attracting compound. The recording materials also contain at least one compound represented by the following formula: STR1 wherein R1 and R3 mean a hydrogen atom or an alkyl, aralkyl or aryl group, R2 and R4 denote an alkyl, alkenyl, aralkyl or aryl group, X1, X2, Y1 and Y2 stand for an oxygen or a sulfur atom, and --Z1 -- and --Z2 -- are a specific aromatic group. Also provided are phenol compounds represented by the following formula: STR2 wherein R1, R2, X1 and Y1 have the same meanings as defined above; R5 and R6 are a hydrogen or halogen atom or an alkyl, alkoxy, aralkyl, aryl or hydroxyl group; p and q stand for an integer of 1-4; R5 and R6 may be either the same or different when p and q represent an integer of 2 or greater; and --Z3 -- means a specific divalent group.
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