Guanine analogues

Another guanine analogue, thioguanine, is also incorporated into both DNA and RNA of mammalian cells [198], and a correlation between its antitumour activity and the extent of its incorporation into DNA has been observed [339,340], although some investigators feel that the metabolic effects of thioguanylic acid may be more universally important [13, 91, 341]. The incorporation of a- and... 

Mutations to loss of activity of this enzyme cause resistance to the guanine analogues 8-azaguanine and 6-thioguanine. Thus, wild-type HPRT " cells can be selected against by incorporation of one of these analogues. 

Bis(hydroxymethyl)phosphonic acid esters that incorporated thymine were employed as a backbone to prepare short oligonucleotide chains. This chain was prepared by condensation of the bis(4,4 -dimethoxytrityl) protected phosphonic acid and iV or N -(2-hydroxyethyl)thymine in the presence of l-(2-mesitylenesul-fonyl)-3-nitro-l,2,4-triazole or by an Appel reaction with or N -(2-aminoethyl)thymine (89a-h). Selective removal of one DMT-group and phos-phitylation yielded the building blocks for solid supported synthesis of the short oligomers by the phosphoramidite approach. Holy has reported the synthesis of 8-amino and 8-substituted amino derivatives of acyclic purine nucleotide analogues. The 8-amino, 8-methylamino- and 8-dimethylamino-adenine and -guanine analogues of iV-(2-phosphonomethoxyethyl) and (S)-iV-(3-hydroxy-2-phosphono-methoxy-propyl) derivatives of purines (90a-i), were prepared by... 

Penciclovir is an acyclic guanine analogue similar to ganciclovir, with in vitro activity against the herpes... 

Adenine has a considerably higher oxidation potential than guanine [111], and for this reason it is not as readily oxidized, even by strongly oxidizing radicals, S04 " excepted. The p a of the adenine radical cation, at less than 1 [5], lies below that of its guanine analogue. 

In the same way as cAMP is formed from ATP by adenylyl cyclase, the guanine analogue, cGMP, can be formed from GTP by guanylyl cyclase. This may be either an integral membrane protein, like adenylyl cyclase, or a cytosolic protein. cGMP is produced in response to a number of neurotransmitters and also nitric oxide, the endothelium-derived relaxation factor that is important in vasodilatation. 

Similarly, the presence of thymine is crucial for a high activity of AZT (3b). The adenine and cytosine derivatives 3c, 3d are substantially less active. The guanine analogue 3a has an anti-HIV effect, although of lower magnitude than the parent compound 3b. Thus, for any new series of analogues, it is wise to prepare all four compounds containing DNA bases unless there are reasons for a different rationale. 

A few C8-modifications have been described, though the main C8-guanine modification is 8-oxoguanine. A C8-(2-pyridyl)guanine analogue has been reported that forms selective binding with Cu(II), Ni(II), Cd(II) and Zn(II) ions via coordination with the guanine N7. An unstable... 

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