Oligonucleotide Conformations

Guanylyl‐3′‐5′‐uridine (GpU) and seventeen GpU analogues modified mostly on the uridine moiety have been investigated by circular dichroism (CD). The following conclusions can be drawn from this investigation. At room temperature and neutral pH GpU is very little, if at all stacked. A perpendicular structure with guanosine in syn and uridine with ϕCN∼+75°± 15°C stabilized by a hydrogen bond between the amino group of guanosine and the C‐4 keto group of uridine is proposed. In this structure C‐5 and C‐6 would be hidden by the guanosine base. At low temperature or low pH stacking occurs. The structure is possibly the same under these conditions and may involve guanosine in syn and uridine in anti. Substitution at C‐5 of uridine inhibits the formation of the neutral perpendicular structure. Seven C‐5 substituted GpU analogues all show CD spectra close to those of GpU at low temperature or low pH. Substitution on C‐6 of uridine destabilizes the formation of all these structures.