排序方式: 共有55条查询结果,搜索用时 15 毫秒
11.
Arielis Estevez Dr. Dongsheng Zhu Connor Blankenship Prof. Jiaoyang Jiang 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(53):12086-12100
The O-linked β-N-acetylglucosamine (O-GlcNAc) modification, termed O-GlcNAcylation, is an essential and dynamic post-translational modification in cells. O-GlcNAc transferase (OGT) installs this modification on serine and threonine residues, whereas O-GlcNAcase (OGA) hydrolyzes it. O-GlcNAc modifications are found on thousands of intracellular proteins involved in diverse biological processes. Dysregulation of O-GlcNAcylation and O-GlcNAc cycling enzymes has been detected in many diseases, including cancer, diabetes, cardiovascular and neurodegenerative diseases. Here, recent advances in the development of molecular tools to investigate OGT and OGA functions and substrate recognition are discussed. New chemical approaches to study O-GlcNAc dynamics and its potential roles in the immune system are also highlighted. It is hoped that this minireview will encourage more research in these areas to advance the understanding of O-GlcNAc in biology and diseases. 相似文献
12.
O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is directly associated with the level of O-GlcNAc glycosylation of biomolecules and various diseases, and it is expected to be a promising potential new therapeutic target. Here, we develop a robust and sensitive method for OGT assay based on capillary electrophoresis-laser induced fluorescence (CE-LIF) method. AF-488-modified peptide containing serine active group is designed as substrate for OGT-catalyzed reaction, and nonradioactive UDP-GlcNAc is employed as sugar donor to perform O-GlcNAc glycosylation modification. The enzyme activity of OGT is measured by quantitative determination of glycosylated peptide produced by the reaction. Large volume sample stacking technique for sample injection and a unique fluorescence collection system for LIF detection are adopted to greatly enhance the detection sensitivity, thus a low limit of detection down to 0.23 pM for OGT detection is achieved. The method is successfully applied to detect OGT activity in clinical blood samples with satisfactory accuracy. Our study provides a simple, accurate, and sensitive method with great potential application in clinical diagnosis of O-GlcNAc-related diseases. 相似文献
13.
Matthew G. Alteen Hayden Peacock Richard W. Meek Jil A. Busmann Sha Zhu Gideon J. Davies Hiroaki Suga David J. Vocadlo 《Angewandte Chemie (International ed. in English)》2023,62(5):e202215671
Glycosyltransferases are a superfamily of enzymes that are notoriously difficult to inhibit. Here we apply an mRNA display technology integrated with genetic code reprogramming, referred to as the RaPID (random non-standard peptides integrated discovery) system, to identify macrocyclic peptides with high binding affinities for O-GlcNAc transferase (OGT). These macrocycles inhibit OGT activity through an allosteric mechanism that is driven by their binding to the tetratricopeptide repeats of OGT. Saturation mutagenesis in a maturation screen using 39 amino acids, including 22 non-canonical residues, led to an improved unnatural macrocycle that is ≈40 times more potent than the parent compound (Kiapp=1.5 nM). Subsequent derivatization delivered a biotinylated derivative that enabled one-step affinity purification of OGT from complex samples. The high potency and novel mechanism of action of these OGT ligands should enable new approaches to elucidate the specificity and regulation of OGT. 相似文献
14.
15.
Gatterdam V Stoess T Menge C Heckel A Tampé R 《Angewandte Chemie (International ed. in English)》2012,51(16):3960-3963
Light, GSH, action! Glutathione (GSH) fulfills a universal role as redox factor, scavenger of reactive oxygen species, and as an essential substrate in the conjugation, detoxification, and reduction reactions catalyzed by glutathione S-transferase (GST). A photoactivatable glutathione allows the GSH-GST network to be triggered by light. GST fusion proteins can be assembled in situ at variable density and structures by laser-scanning activation. 相似文献
16.
《Analytical letters》2012,45(8):850-861
A quick and sensitive detection of the wild-type hypoxanthine guanine phosphoribosyl transferase (HPRT), which is known as a biomarker for radiation exposure, was developed. The conventional HPRT measurement technique is to detect the mutant HPRT, which is time-consuming and has low sensitivity. In this study, the wild-type HPRT was detected as a gamma radiation biomarker using a surface plasmon resonance (SPR) biosensor with 6-thioguanine (6-TG) as a probe and the anti-HPRT antibody as a signal amplification factor. First, we used this system to measure the wild-type HPRT dissolved in PBS. Six-TG immobilized on the surface can specifically detect the wild-type HPRT, and the anti-HPRT antibody enhances about 10 times the primary signal produced by the binding of the wild-type HPRT with 6-TG. A linear relationship (r = 0.991) was obtained between the concentration of the wild-type HPRT and the enhanced signal. The low detection limit (LDL) is 2.1 ng/mL. The regeneration using glycine-HCl was also investigated. Six-TG immobilized on the surface can be used in 9 injection-regeneration cycles. The relative standard deviation (RSD) of baseline changes after regenerations is 2.8%. The applicability of the method to real samples has been demonstrated with comparative analyses of lymphocyte extracts in gamma irradiated and unirradiated mice. The irradiated sample displays a significantly lower level of the wild-type HPRT compared to that in the unirradiated sample. The single sample detection only needs about 20 min. Thus, the SPR biosensor could potentially serve as an attractive technique for rapid and sensitive detection of the wild-type HPRT, a gamma radiation biomarker. 相似文献
17.
Dr. Matthieu Fonvielle Dr. Inés Li de La Sierra‐Gallay Dr. Afaf H. El‐Sagheer Maxime Lecerf Delphine Patin Dr. Dénia Mellal Dr. Claudine Mayer Dr. Didier Blanot Dr. Nittaya Gale Dr. Tom Brown Dr. Herman van Tilbeurgh Dr. Mélanie Ethève‐Quelquejeu Dr. Michel Arthur 《Angewandte Chemie (International ed. in English)》2013,52(28):7278-7281
18.
19.
Lalrempuia R Müller-Bunz H Albrecht M 《Angewandte Chemie (International ed. in English)》2011,50(42):9969-9972
Hop on, hop off: An iridium center transfers a methyl group from pyridinium to an aryl unit, using exclusively the pyridine-bound methyl group as a mild methylene source. The reaction also involves cleavage of an unactivated C(aryl)?H bond and nitrile solvent activation. The process is reminiscent of DNA methylation and entails the formation of two new C(sp(2) )?C(sp(3) ) bonds within the metal coordination sphere. 相似文献
20.
Mirza UA Chen G Liu YH Doll RJ Girijavallabhan VM Ganguly AK Pramanik BN 《Journal of mass spectrometry : JMS》2008,43(10):1393-1401
Farnesyl protein transferase (FPT) inhibition is an interesting and promising approach to noncytotoxic anticancer therapy. Research in this area has resulted in several orally active compounds that are in clinical trials. Electrospray ionization (ESI) time-of-flight mass spectrometry (TOF-MS) was used for the direct detection of a 95 182 Da pentameric noncovalent complex of alpha/beta subunits of FPT containing Zn, farnesyl pyrophosphate (FPP) and SCH 66336, a compound currently undergoing phase III clinical trials as an anticancer agent. It was noted that the desalting of protein samples was an important factor in the detection of the complex. This study demonstrated that the presence of FPP in the system was necessary for the detection of the FPT-inhibitor complex. No pentameric complex was detected in the spectrum when the experiment was carried out in the absence of the FPP. An indirect approach was also applied to confirm the noncovalent binding of SCH 66336 to FPT by the use of an off-line size exclusion chromatography followed by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) for the detection of the inhibitor. 相似文献