N-Glycoside bond

Steric hindrance by the base restricts rotation about the P-N-glycosidic bond of nucleosides and nu-... 

Posttranslational modification of preformed polynucleotides can generate additional bases such as pseudouridine, in which D-ribose is linked to C-5 of uracil by a carbon-to-carbon bond rather than by a P-N-glycosidic bond. The nucleotide pseudouridylic acid T arises by rearrangement of UMP of a preformed tRNA. Similarly, methylation by S-adenosylmethionine of a UMP of preformed tRNA forms TMP (thymidine monophosphate), which contains ribose rather than de-oxyribose. 

The depurination of DNA, which happens spontaneously owing to the thermal lability of the purine N-glycosidic bond, occurs at a rate of 5000-10,000/cell/d at 37 °C. Specific enzymes recognize a depurinated site and replace the appropriate purine directly, without interruption of the phosphodiester backbone. 

Figure 1.39 The formation of an N-glycosidic bond links the base unit of nucleic acids to the associated ribose derivative.

In the carbohydrate chemistry arena, the Tsuji-Trost reaction has been applied to construct N-glycosidic bonds [53]. In the presence of Pd2(dba>3, the reaction of 2,3-unsaturated hexopyranoside 68 and imidazole afforded N-glycopyranoside 69 regiospecifically at the anomeric center with retention of configuration. In terms of the stereochemistry, the oxidative addition of allylic substrate 68 to Pd(0) formed the jc-allyl complex with inversion of configuration, then nucleophilic attack by imidazole proceeded with another inversion of the configuration. Therefore, the overall stereochemical outcome is retention of configuration. 

The base adenine is bound to C-1 of ribose by an N-glycosidic bond (see p.36). In addition to C-2 to C-4, C-1 of ribose also represents a chiral center. The p-configuration is usually found in nucleotides. 

In nucleosides and nucleotides, the pentose residues are present in the furanose form (see p.34). The sugars and bases are linked by an N-glycosidic bond between the C-1 of the sugar and either the N-9 of the purine ring or N-1 of the pyrimidine ring. This bond always adopts the p-conflguration. 

Both 11P-HSD types 1 and 2 contain residues in the C-terminal half that interact with the nicotinamide ring and carboxamide moiety to limit rotations about the N-glycosidic bond. These intersections are important in positioning the cofactor for proS hydride transfer at C4. 

Depurination, or hydrolysis of the N-glycosidic bond, occurs for both RNA and DNA strands (oligomers/polymers) or analogs (monomers). RNA is much less prone to depurination than DNA as a result of the inductive effect of the 2 -OH group (180). Acid-catalyzed depurination is illustrated in Figure 129. 

N-linked oligosaccharides are linked to the protein via N-glycosidic bonds, to the NH2 groups of asparagine side chains (Fig. lb) where the asparagine occurs in the sequence Asn-X-Ser (or Thr) where X is any amino acid except Pro and possibly Asp. 

N-linked oligosaccharides attached to the protein via N-glycosidic bonds,... 

This is the most widely studied structural form of glycosylation and has the greatest effect on overall protein structure and function (Kornfeld and Kornfeld, 1985 Spellman, 1990). The glycan consists of a core pentasaccharide (Man3GlcNAc2) attached via an N-glycosidic bond to an Asn residue of a consensus amino acid sequence (sequon) Asn-X-Ser/Thr, where X can be any amino acid except pro line (Figure 6.1). 

By simulating evolution in vitro it has become possible to isolate artificial ribozymes from synthetic combinatorial RNA libraries [1, 2]. This approach has great potential for many reasons. First, this strategy enables generation of catalysts that accelerate a variety of chemical reactions, e.g. amide bond formation, N-glycosidic bond formation, or Michael reactions. This combinatorial approach is a powerful tool for catalysis research, because neither prior knowledge of structural prerequisites or reaction mechanisms nor laborious trial-and-error syntheses are necessary (also for non-enzymatic reactions, as discussed in Chapter 5.4). The iterative procedure of in-vitro selection enables handling of up to 1016 different compounds... 

Protection of amino groups. The o-nitrobenzenesulfenyl (NPS) group is useful for protection of terminal amino groups of peptides and the exocyclic amino groups of bases such as adenine. The group also increases the stability of an N-glycoside bond. It is removable by reduction with Bu3P in aqueous dioxane.12 It is also stable to phosphorylation. These properties have been used to synthesize... 

Figure 10.21 Relationship of deoxyribose and the guanine base in B- and Z-DNA. Rotation to affect either the syn or the anti conformations is done about the N-glycoside bond, as shown by the curved arrow. Also note that in Z-DNA, the 3 carbon is above the plane of the sugar, whereas in B-DNA, the 2 carbon is. This is the endo conformation. (Reproduced by permission from Rich A, Nordheim A, Wang AHJ. The chemistry and biology of left-handed Z-DNA. Annu Rev Biochem 53 701-846, 1984.)...

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