Chemical probing

Parks E K, Welller B H, Bechthold P S, Hoffman W F, NIeman G C, Pobo L G and Riley S J 1988 Chemical probes of metal cluster structure reactions of Iron clusters with hydrogen, ammonia and water J. Chem. Rhys. 88 1622... 

Vignais, P. V., and Lunardi, J., 1985. Chemical probes of mitochondrial ATP. synthe.sis and translocation. Annual Review of Biochemistry 54 977-1014. 

NMR methods can be applied to give quantitative determination of initiator-derived and other end groups and provide a wealth of information on the polymerization process. They provide a chemical probe of the detailed initiation mechanism and a greater understanding of polymer properties. The main advantage of NMR methods over alternative techniques for initiator residue detection is that NMR signals (in particular nC NMR) are extremely sensitive to the structural environment of the initiator residue. This means that functionality formed by tail addition, head addition, transfer to initiator or primary radical termination, and various initiator-derived byproducts can be distinguished. 

We have explored rare earth oxide-modified amorphous silica-aluminas as "permanent" intermediate strength acids used as supports for bifunctional catalysts. The addition of well dispersed weakly basic rare earth oxides "titrates" the stronger acid sites of amorphous silica-alumina and lowers the acid strength to the level shown by halided aluminas. Physical and chemical probes, as well as model olefin and paraffin isomerization reactions show that acid strength can be adjusted close to that of chlorided and fluorided aluminas. Metal activity is inhibited relative to halided alumina catalysts, which limits the direct metal-catalyzed dehydrocyclization reactions during paraffin reforming but does not interfere with hydroisomerization reactions. 

Attard GA, Ahmadi A. 1995. Anion-surface interactions. Part 3 N2O reduction as a chemical probe of the local potential of zero total charge. J Electroanal Chem 389 175-190. 

Unfortunately, we do not have microinterface voltmeters, and we can use only indirect methods like various chemical probes and electrokinetic methods. These methods make it possible to estimate only part of the Galvani potential, denoted here Aj[Pg.35]

The power of the pooled GST fusion protein approach will increase as new biochemical reagents and assays become available. The development of chemical probes for biological processes, termed chemical biology, is a rapidly advancing field. For example, the chemical synthesis of an active site directed probe for identification of members of the serine hydrolase enzyme family has recently been described (Liu et al., 1999). The activity of the probe is based on the potent and irreversible inhibition of serine hydrolases by fluorophosphate (FP) derivatives such as diisopropyl fluorophosphate. The probe consists of a biotinylated long-chain fluorophosphonate, called FP-biotin (Liu et al., 1999). The FP-biotin was tested on crude tissue extracts from various organs of the rat. These experiments showed that the reagent can react with numerous serine hydrolases in crude extracts and can detect enzymes at subnanomolar... 

As in all eukaryotic cells, protein kinases play an important role in the life cycle of the kinetoplastids and, as such, are attractive targets. Recent efforts, predominantly through genetic (RNAi) means, have validated a number of kinases as essential for survival of T. brucei, but few have been explored with chemical probes [33-35]. 

With this evidence of disease relevance, discovering and developing high-quality chemical probes [23] of PMTs has been gaining momentum in both the academic research community and the pharmaceutical industry. Progress in this area is keenly awaited. 

While VFPs have boosted the applications of FRET-FLIM, chemical FRET probes should not be dismissed. The advantage of chemical probes is that they are much smaller in size and that they often have much better spectral readout than VFP probes. In Chapter 6, Amanda Cobos Correa and Carsten Schultz highlight the various small molecule-based FRET probes and their use in bioimaging. 

O Hare, H. M., Johnsson, K. and Gautier, A. (2007). Chemical probes shed light on protein function. Curr. Opin. Struct. Biol. 17, 488-94. 

Polina R.J., Klainer S.M., A field-hardened, optical waveguide hybrid integrated-circuit, multi-sensor chemical probe and its chemistry, Proc. SPIE-Int. Soc. Opt. Eng. 1997 3105 71... 

When suitable data sets are defined, different approaches can be used to codify the chemical information within chemical descriptors. Nowadays we have powerful tools to describe them in different ways by their physicochemical properties, surface properties, or their 3D fields generated by interactions with different chemical probes. Typically many chemical descriptors are calculated (up to thousands) and then the important ones are selected. We briefly explain some of the most common approaches used, trying to classify them in families to simplify the overview. 

Lomant, A.J., and Fairbanks, G. (1976) Chemical probes of extended biological structures synthesis and properties of the cleavable cross-linking reagent [35S] dithiobis(succinimidyl propionate)./. Mol. Biol. 104, 243-261. 

Zhang, H., Yan, W., and Aebersold, R. (2004) Chemical probes and tandem mass spectrometry A strategy for the quantitative analysis of proteomes and subproteomes. Curr. Opin. Chem. Biol. 8, 66-75. 

Further experiments focused therefore on [RuCl(en)(r 6-tha)]+ (12) and [RuCl(rj6-p-cym)(en)]+ (22), which represent the two different classes, and their conformational distortion of short oligonucleotide duplexes. Chemical probes demonstrated that the induced distortion extended over at least seven base pairs for [RuCl(rj6-p-cym)(en)]+ (22), whereas the distortion was less extensive for [RuCl(en)(rj6-tha)]+ (12). Isothermal titration calorimetry also showed that the thermodynamic destabilization of the duplex was more pronounced for [RuCl(r 6-p-cym)(en)]+ (22) (89). DNA polymerization was markedly more strongly inhibited by the monofunctional Ru(II) adducts than by monofunctional Pt(II) compounds. The lack of recognition of the DNA monofunctional adducts by HMGB1, an interaction that shields cisplatin-DNA adducts from repair, points to a different mechanism of antitumor activity for the ruthenium-arenes. DNA repair activity by a repair-proficient HeLa cell-free extract (CFE) showed a considerably lower level of damage-induced DNA repair synthesis (about six times) for [RuCl(en)(rj6-tha)] + compared to cisplatin. This enhanced persistence of the adduct is consistent with the higher cytotoxicity of this compound (89). 

Newton MD (1991) Quantum chemical probes of electron-transfer kinetics the nature of donor-acceptor interactions. Chem Rev 91 767-792... 

The Molecular Libraries Screening Center Network (MLSCN) Identifying Chemical Probes of Biological Systems... 

Each screening center has medicinal and synthetic chemistry expertise in order to optimize hits identified from HTS campaigns and develop them into chemical probes. Specific capabilities vary, however typical strategies employed include parallel synthesis, computational and informatics analysis, and analytical capabilities such as LC/MS techniques. The structures of novel compounds that are prepared, their synthetic protocols, analytical data and biological data are all available, and samples of final probes developed are deposited into the MLSMR. A Working Group comprised of chemists from each center meets regularly to share information, best practices, and insure optimal use of resources. 

Access to modified nucleosides. Base-modified nucleosides and nucleotides are very important for their biological properties. They can be found as antiviral agents (HBH, VZV, AIDS),93 95 in the study of DNA degradation,96,97 as fluorescent agents and as chemical probes of DNA structure.98 101 The access to nucleosides can be achieved by different methods ... 

Chemical probes such as titrations using Hammett indicators [188,189] and test reactions [190] have been often employed as well. Given that each method has its own strengths and limitations, a rational combination of specific techniques is often the best approach to the study of a given catalytic system. 

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