N-Glycosyl linkage

III. Structural Analysis of Glycopeptides and Glycoproteins Containing N-Glycosyl Linkages... 

These observations have several implications for studies of glycoproteins (i) the resonances of anomeric carbon atoms that are involved in N-glycosylic linkages will be rather difficult to identify, because of their proximity to nonanomeric-carbon resonances and (ii) due to the proximity of the chemical shifts of C-l and C-5 (they are only 0.6 p.p.m. apart for / -d-G1cNAc — Asn), it may be difficult, but not impossible, to ascertain whether N-glycosylic linkages exist in the glycoprotein (see later). 

Radical-induced Scission of the Glycosidic or N-Glycosyl Linkage. 51... 

The sequence of amino acids around the N-glycosyl linkages in glycoenzymes and glycoproteins is generally of the following type ... 

Several spontaneous hydrolytic reactions also cause DNA damage. For example, it has been estimated that several thousand purine bases are lost daily from the DNA in each human cell. In depurination reactions the N-glycosyl linkage between a purine base and deoxyribose is cleaved. The protonation of N-3 and N-7 of guanine promotes hydrolysis. If repair mechanisms do not replace the purine nucleotide, a point mutation will result in the next round of DNA replication. Similarly, bases can be spontaneously deaminated. For example, the deaminated product of cytosine converts to uracil via a tautomeric shift. Eventually, what should be a CG base pair is converted to an AT base pair. (Uracil is similar in structure to thymine.)... 

Base excision repair (BER). The N-glycosyl linkages of the pmine and pyrimidine bases to the deox-ribose residues of the sugar-phosphate backbone of DNA are subjecf to sponfaneous hydrolysis, one important source of damage to DNA. Similar hydrolytic reactions are catalyzed by DNA glycosylases, which remove many mismatched or damaged bases. " ... 

Moreover, where studied (3,i), the 2 -fluoro nucleosides were resistant to catabolic cleavage by nucleoside phosphorylases, presumably a result of the increased metabolic stability of the N-glycosyl linkage imposed by this electronegative 2 -substituent. Of the several 2 -fluoro—5-substituted—arabinosyl pyrimidine nucleosides synthesized (1.), l-(2 -deozy-2 -fluoro-3-D-arabinofuranosy 1 )-5-iodo-cytosine [FIAC] has demonstrated clinical efficacy against Herpesvirus infections in Phase 1 (5,) and against Varicella zoster virus in Phase 2 ( ) clinical trials in immunocompromised cancer patients. 

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