Modified attachment chemistry

In ihis chapter you continue to study the chemistry of aromatic compounds. You find out about reactions at a carbon attached to a benzene ring (a bcnzylic carbon) and about more transformations of benzenes containing either liydroxy or amino groups connected directly to th" rmg. In all the.se ca.ses the interaction of the benzene ring with the attached groups modifies their chemistry significantly. 

An alternative to modifying the functional group attached to fibrils is to utilise the chemistry present in the amino acid side chains. Furthermore, as peptides often undergo specific modification by enzymes in vivo, these could be harnessed for synthetic purposes. Qll (Ac-QQKFQFQFEQQ-Am, a fibril-forming peptide based on Pi 1-2), was coupled to lysine-based molecules by treatment with an enzyme (tissue transglutaminase, TGase) which results in a reaction between lysine and glutamine side chains [72] (Fig. 32). 

The initial hurdle to overcome in the biosensor application of a nucleic acid is that involving its stable attachment on a transducing element which commonly includes a metallic electrode. In the first part of this chapter, we wish to introduce our approach for DNA immobilization (Scheme 1). A detailed characterization of the immobilization chemistry is also presented. In the second part, we follow the development of work from our laboratory on chemical sensor applications of the DNA-modified electrode involving a biosensor for DNA-binding molecules and an electrochemical gene sensor. 

Smith and co-workers (194) have used this chemistry to prepare carboxyl-modified Si(lll) surfaces at which polylysine-tethered DNA is electrostatically adsorbed (Fig. 60). An alternative approach involved covalent attachment of a pre-synthesized oligonucleotide bearing a terminal carboxyl group to an amine-modified Si(001) surface (195). 

MW heated reactions in homogeneous media, using either neat reagents or in the presence of solvents, may also be performed at atmospheric pressure. This approach has been used particularly by Bose et al. [17]. (MORE Chemistry), who reported, for example, the rapid synthesis of heterocycles [18] in open vessels. Another approach, which avoids hazards due to the flammability of solvents, is to perform the reactions under reflux in a MW oven, which is modified to allow the reaction vessel to be attached to a reflux condenser outside the MW oven [7, 19]. It should be pointed out, however, that most of the available evidence shows that rate enhancements of MW heated reactions in homogeneous media at atmospheric pressure are small or nonexistent [19], This will be discussed in more detail later in this review (see also Chapt. 5 of this book). 

C60 is also a highly versatile synthetic scaffold that can easily be functionalized by the methods of synthetic organic chemistry. The formation of C60 derivatives (i.e., covalently modified C60) nearly always involves the addition of a functional group (addend) across one or more of its 30 double bonds. When only one addend is attached, the fullerene derivative is called a monoadduct, with two, a bisadduct, etc. The ability to sensitize molecular oxygen in the presence of visible light is retained in the simple derivatives of C60 (i.e., mono-, bis-, and trisadducts). 

Some enzymes are nonfunctional until posttranslationally modified. Examples of these enzymes include the acyl- and carboxyltransferases. While lipoate and phosphopantetheine are necessary for acyl transfer chemistry, tethered biotin is used in carboxyl transfer chemistry. Biotin and lipoate tethering occur under a similar mechanism the natural small molecule is activated with ATP to form biotinyl-AMP or lipoyl-AMP (Scheme 20). A lysine from the target protein then attacks the activated acid and transfers the group to the protein. The phosphopantetheine moiety is transferred using its own enzyme, the phosphopantetheinyltrans-ferase (PPTase). The PPTase uses a nucleophilic hydroxy-containing amino acid, serine, to attach the phosphopantetheinyl (Ppant) arm found in coenzyme A to convert the apo (inactive) carrier protein to its holo (active) form. The reaction is Mg -dependent. 

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