35444-44-1Relevant articles and documents
An antibody-catalyzed isomerization reaction
Uno,Ku,Prudent,Huang,Schultz
, p. 3811 - 3817 (1996)
Monoclonal antibodies (mAbs) were generated against the coplanar transition state (TS(paragraph)) analogue 1 and assayed for their ability to catalyze the isomerization of bridged biphenyls 4, 6, and 7. This is a relatively simple unimolecular reaction whose activation barrier arises from unfavorable steric interactions between the two benzylic methylene groups and strain in the bridging ring system. Seven mAbs were found that catalyzed the isomerization of 4 to 6; the most efficient (mAb 64D8E10) has k(cat) and K(M) values of 4.3 x 10-5 s-1 and 420 μM, respectively. This corresponds to a rate enhancement over the unimolecular uncatalyzed reaction (k(cat)/k(uncat)) of 2900. The dissociation constant for the TS(paragraph) analogue, K(d), was determined to be 210 nM. For both the antibody (64D8E10) catalyzed and uncatalyzed reactions, the free energy of activation (ΔG(paragraph)) is comprised largely of the enthalpy term; the antibody decreases the enthalpy of activation by 5 kcal/mol. Despite relatively large differences in the values of k(cat)/k(uncat) for the five antibodies, the ratios of K(d) to K(M)(4) are very similar. It is likely that the antibodies catalyze this reaction by reducing both ring strain and nonbonded steric interactions in the transition state.
ω-oxidation of α-chlorinated fatty acids: Identification of α-chlorinated dicarboxylic acids
Brahmbhatt, Viral V.,Albert, Carolyn J.,Anbukumar, Dhanalakshmi S.,Cunningham, Bryce A.,Neumann, William L.,Ford, David A.
, p. 41255 - 41269 (2010)
Myeloperoxidase-derived HOCl targets tissue- and lipoprotein- associated plasmalogens to generate α-chlorinated fatty aldehydes, including 2-chlorohexadecanal. Under physiological conditions, 2-chlorohexadecanal is oxidized to 2-chlorohexadecanoic acid (2-ClHA). This study demonstrates the catabolism of 2-ClHA by ω-oxidation and subsequent β-oxidation from the ω-end. Mass spectrometric analyses revealed that 2-ClHA is ω-oxidized in the presence of liver microsomes with initial ω-hydroxylation of 2-ClHA. Subsequent oxidation steps were examined in a human hepatocellular cell line (HepG2). Three different α-chlorinated dicarboxylic acids, 2-chlorohexadecane-(1,16)- dioic acid, 2-chlorotetradecane- (1,14)-dioic acid, and 2-chloroadipic acid (2-ClAdA), were identified. Levels of 2-chlorohexadecane-( 1,16)-dioic acid, 2-chlorotetradecane-(1,14)-dioic acid, and 2-ClAdA produced by HepG2 cells were dependent on the concentration of 2-ClHA and the incubation time. Synthetic stable isotope-labeled 2-ClHA was used to demonstrate a precursorproduct relationship between 2-ClHA and the α-chlorinated dicarboxylic acids. We also report the identification of endogenous 2-ClAdA in human and rat urine and elevations in stable isotopelabeled urinary 2-ClAdA in rats subjected to intraperitoneal administration of stable isotope-labeled 2-ClHA. Furthermore, urinary 2-ClAdA and plasma 2-ClHA levels are increased in LPStreated rats. Taken together, these data show that 2-ClHA is ω-oxidized to generate α-chlorinated dicarboxylic acids, which include α-chloroadipic acid that is excreted in the urine.
A synthesis and properties of new 4,4-difluoro-3a,4a- diaza-s-indacene (BODIPY)-labeled lipids
Boldyrev,Molotkovsky, Jul G.
, p. 78 - 83 (2006)
A series of fluorescently labeled fatty acids of various chain lengths with 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene-8-yl (Me 4-BODIPY-8) residue in the ω-position were synthesized. These acids were used to prepare new fluorescently labeled phosphatidylcholines, sphingomyelin, and galactosyl ceramide. The symmetry of the Me 4-BODIPY-8-fluorophore suggests that, in most bilayer membrane systems, this fluorophore would be embedded into the bilayer. Pleiades Publishing, Inc., 2006.
BODIPYs revealing lipid droplets as valuable targets for photodynamic theragnosis
Agarrabeitia, Antonia R.,De La Moya, Santiago,García-Garrido, Fernando,García-Moreno, Inmaculada,Ortiz, María J.,Palao, Eduardo,Prieto-Casta?eda, Alejandro,Tabero, Andrea,Villanueva, Angeles
, p. 940 - 943 (2020)
Endowing BODIPY PDT agents with the ability to probe lipid droplets is demonstrated to boost their phototoxicity, allowing the efficient use of highly fluorescent dyes (poor ROS sensitizers) as phototoxic agents. Conversely, this fact opens the way to the development of highly bright ROS photosensitizers for performing photodynamic theragnosis (fluorescence bioimaging and photodynamic therapy) from a single simple agent. On the other hand, the noticeable capability of some of the reported dyes to probe lipid droplets in different cell lines under different conditions reveals their use as privileged probes for advancing the study of interesting lipid droplets by fluorescence microscopy.
Synthesis of the 4-aza cyclopentenone analogue of Δ12,14-15-deoxy-PGJ2 and S-cysteine adducts
Conway, Lorna,Riccio, Anna,Santoro, M. Gabriella,Evans, Paul
, (2020)
The synthesis of a series of 4-aza cross-conjugated cyclopentenones, inspired by the natural prostaglandin Δ12,14-15-deoxy-PGJ2 (5) is described. Using the 4-aza cyclopentenone 7, the installation of the α-side chain was performed using N-functionalisation, following a Boc-deprotection. The ω-side chain was then installed through a Baylis-Hillman type aldol reaction with trans-2-octenal. This afforded 11, the aza-analogue of 5. With this prostaglandin analogue in hand, a series of thiol adducts (14–16) were prepared. Included are activities for compounds 11 and 14–16 in relation to inhibition of the transcription factor NF-κB.
New protoilludane sesquiterpenes from Lactarius violascens
Vidari, Giovanni,Garlaschelli, Luigi,Rossi, Alessandra,Vita-Finzi, Paola
, p. 1957 - 1960 (1998)
Violascensol 1 and the corresponding 6-ketostearoyl ester 2 were isolated from the fruiting bodies of Lactarius violascens. Their structures were established by spectroscopic and chemical methods. Compounds 1 and 2 are the first examples of protoilludane sesquiterpenes isolated from a Lactarius species.
Neutrophil-Selective Fluorescent Probe Development through Metabolism-Oriented Live-Cell Distinction
Gao, Min,Lee, Sun Hyeok,Park, Sang Hyuk,Ciaramicoli, Larissa Miasiro,Kwon, Haw-Young,Cho, Heewon,Jeong, Joseph,Chang, Young-Tae
supporting information, p. 23743 - 23749 (2021/10/14)
Human neutrophils are the most abundant leukocytes and have been considered as the first line of defence in the innate immune system. Selective imaging of live neutrophils will facilitate the in situ study of neutrophils in infection or inflammation events as well as clinical diagnosis. However, small-molecule-based probes for the discrimination of live neutrophils among different granulocytes in human blood have yet to be reported. Herein, we report the first fluorescent probe NeutropG for the specific distinction and imaging of active neutrophils. The selective staining mechanism of NeutropG is elucidated as metabolism-oriented live-cell distinction (MOLD) through lipid droplet biogenesis with the help of ACSL and DGAT. Finally, NeutropG is applied to accurately quantify neutrophil levels in fresh blood samples by showing a high correlation with the current clinical method.
Aziridine-2-carboxylic acid derivatives and its open-ring isomers as a novel PDIA1 inhibitors
Leite, Irena,Andrianov, Victor,Zelencova-Gopejenko, Diana,Loza, Einars,Kazhoka-Lapsa, Iveta,Domracheva, Ilona,Stoyak, Marta,Chlopicki, Stefan,Kalvins, Ivars
, p. 1086 - 1106 (2022/01/12)
[Figure not available: see fulltext.] Acyl derivatives of aziridine-2-carboxylic acid have been synthesized and tested as PDIA1 inhibitors. Calculations of charge value and distribution in aziridine ring system and some alkylating agents were performed. For the first time was found that acyl derivatives of aziridine-2-carboxylic acid are weak to moderately active PDIA1 inhibitors.
Design, synthesis and biological evaluation of novel indazole-based derivatives as potent HDAC inhibitors via fragment-based virtual screening
Gao, Liang,Gao, Lina,He, Fengjun,Hu, Lihong,Kang, Di,Liu, Jian,Wang, Ping,Wen, Yu,Zhou, Jingxian
, (2020/03/10)
Based on fragment-based virtual screening and bioisoterism strategies, novel indazole and pyrazolo[3,4-b] pyridine derivatives as HDACs inhibitors were designed, synthesized and evaluated. Most of these compounds displayed good to excellent inhibitory activities against HDACs, especially compounds 15k and 15m were identified as potent inhibitors of HDAC1 (IC50 = 2.7 nM and IC50 = 3.1 nM), HDAC2 (IC50 = 4.2 nM and IC50 = 3.6 nM) and HDAC8 (IC50 = 3.6 nM and IC50 = 3.3 nM). Further anti-proliferation assays revealed that compounds 15k and 15m showed better anti-proliferative activities against HCT-116 and HeLa cells than positive control SAHA. The western blot analysis results indicated that compounds 15k and 15m noticeably up-regulated the level of acetylated α-tubulin and histone H3. In addition, the two compounds 15k and 15m could arrest cell cycle in G2/M phase and promote cell apoptosis, which was similar as the reference compound SAHA. Through the molecular docking and dynamic studies, the potent HDAC inhibitory activities mainly caused by van der Waals and electrostatic interactions with the HDACs.
Cationic lipid molecule, and application thereof in nucleic acid delivery
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Paragraph 0149-0152, (2019/10/08)
The present invention discloses a cationic lipid molecule, and an application thereof in nucleic acid delivery. The structural formula of the cationic lipid molecule is represented by formula i. The invention further provides a cationic liposome, a lipid compound, a reagent, a kit, a preparation and a medicinal composition based on the cationic lipid molecule. The cationic lipid molecule has the advantages of simple synthesis process and good stability, and the cationic liposome has a high efficiency (characterized by high transfection efficiency) and a low toxicity, is stable and uniform, is easy to prepare, and can be used for transferring various cell lines. The cationic lipid molecule has excellent transitivity, and can efficiently deliver active substances (such as exemplary siRNA) omto cells (such as exemplary lung cancer cells), tissues and organs to achieve efficient regulation of the active substances. The problem that the toxicity and the transfer efficiency of cationic liposome existing in the prior art are low is solved.
