An ellipticine derivative (oxazolopyridocarbazolium) 3′ linked to tetrathymidylate stacks intramolecularly with the nearest thymine at low concentration and head‐to‐tail intermolecularly at high concentration

Abstract

The solution conformation of a tetrathymidylate linked through an ester bond to an ellipticine derivative oxazolopyridocarbazolium (OPC) at the 3' position was investigated using one- and two-dimensional nmr experiments. Since the total electric charge of the OPC ring may influence self-association, we first determined the pKa of the oxazole cyclic acidic function. Nuclear Overhauser effect spectroscopy experiments showed that, at low concentration, the OPC stacks intramolecularly with the nearest thymine at the 3' end. At highest concentration, however, the OPC rings are self-associated. The stacking constant was calculated using 1H chemical shift dilution experiment. The conformational model suggested by P-nmr was tested by molecular mechanics computations.

Triple Helix Formation with Short Oligonucleotide-Intercalator Conjugates Matching the HIV-1 U3 LTR End Sequence

“…We built a triple helix d(GGAA-GGGCTAAT)-d(CCCTTCCGATTA).d(GGGAAGG) (Figure 1) using OCL (Gabarro-Arpa et al, 1992) and an automated builder module included in the program MORCAD (Le Bret et al, 1991) running on a Silicon Graphics Iris 4D310. The coordinates of OPC are derived from X-ray data concerning ellipticine (Courseille et al, 1981) as performed in a previous work (Bazile et al, 1990). The OPC was set parallel or perpendicular in one of the five sites between G7 and T12.…”