Tautomeric equilibrium of 1-?-D-ribofuranosyl-2-keto-4-(n-methoxyamino)pyrimidine

Hydroxylamine and methoxyamine mutagenesis: displacement of the tautomeric equilibrium of the promutagen N6-methoxyadenosine by complementary base pairing

“…A similar situation is encountered with Ar4-hydroxy-and Ar4-methoxycytidines, detectable only in the imino form in low-polar solvents (Brown et al, 1968), in the gas phase (Kulinska et al, 1980), and iri the solid state (Shugar et al, 1976;Birnbaum et al, 1979). The imino form, although predominant in polar media like water, is reported to be in equilibrium with from 10% (Brown et al, 1968) to 25% (Sverdlov et al, 1971) of the amino species, and this is reflected, as in the case of A^-methoxyadenosine, by its dual functional properties in polymerase systems where, both as a free triphosphate substrate or when located in a template (Budowsky et al, 1971b;Flavell et al, 1974), it comports itself like uridine or cytidine. However, at the monomer level in chloroform solution, it does not form Watson-Crick base pairs with either adenosine or guanosine because of the syn conformation, relative to the ring N(3), of the exocyclic Ar4hydroxy (or methoxy) group (Kierdaszuk & Shugar, 1983a).…”

“…The subsequent demonstration that these mutagens also react with adenosine residues, albeit more slowly, to give the A^-hydroxy-and A^-methoxyadenosines [for review see Budowsky (1976)] suggested the need for an investigation of the tautomerism and base pairing properties of these analogues. This is further indicated by the fact that A^-hydroxyadenine is a promutagenic analogue in the rll mutant system of phage T4 (Freese, 1968), in which it behaves like adenine or guanine, and that in an in vitro transcription system, A^-methoxyadenosine residues paired with both U and C,1 but not A and G (Singer & Spengler, 1982); i.e., these residues exhibit dual functional properties in base pairing, like 7V4-hydroxycytidine residues (Budowsky et al, 1971a;Flavell et al, 1974), which exist in aqueous medium as a mixture of two tautomers (Brown et al, 1968;Sverdlov et al, 1971). However, as in the case of Ar4-hydroxycytosines, or methoxycytosines, the base pairing properties of the two tautomeric forms of A*-hydroxyadenosines, or methoxyadenosines, will also depend on the orientation of the N6-OH or N6-OCH3 tFrom the Department of Biophysics, Institute of Experimental Physics, University of Warsaw, 02-089 Warszawa, Poland (R.S., B.K., and D.S.…”

Addition of Amino Acids and Related Substances to Nucleic Acids by Nucleophilic Catalysis

“…3. The rightmost (oxime) tautomer is predominant (Brown et at., 1968;Sverdlov et al, 1971). In this form.…”