Essay about Effect Of The 2 ′ -oh

1764 Words Nov 29th, 2016 8 Pages
It is also conceivable that, at lower pH, depurination can occur via protonation of the purine nucleobase at both N1 and N7. The presence of the 2′-OH has a significant effect on the nucleoside’s susceptibility to depurination. For example, guanosine and adenosine are more resistant to depurination compared to deoxyadenosine and deoxyguanosine. Deoxyadenosine itself depurinates 1200 times faster than adenosine (York, 1981).
Interestingly, N-acyl-protected purine nucleosides (particularly deoxyadenosine) are more prone to depurination than unprotected nucleosides. Among N-acyl-protected deoxyadenosines, protection at N6 with α-phenylcinnamoyl, naphthaloyl, 3-methoxy-4-phenoxybenzoyl, 9-fluorenylmethoxycarbonyl (FMOC), and tert-butylphenoxyacetyl (t-PAC) groups (Figure 2.1.7) provides greater resistance to depurination than with N6-benzoyl (reviewed in Beaucage and Iyer, 1992). It is believed that in the case of acyl-protected purine nucleosides under acidic conditions, the initial site of protonation is N7, rendering the protonated species more prone to glycosidic cleavage. Naturally, caution should be exercised in the synthesis of oligonucleotides whose sequence contains deoxyadenosines at the 3′ terminus.
Bis-acylation has also been studied as a strategy to reduce depurination. Imide protecting groups S.16, S.17, S.18, and S.19 as well as the diamide protecting group S.20, have been investigated (Figure 2.1.9; Kume et al., 1982 and 1984, Tusnoda et al., 2010). However,…

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