2,5-Bis(4-guanylphenyl)furan ("furamidine") is a dicationic minor groove binding drug that has been shown to be more effective than pentamidine against the Pneumocystis carinii pathogen in an immunosuppressed rat model. It has a close structural similarity to the antitrypanosomal drug berenil, differing only on the replacement of the central triazene unit with a furan moiety. we have determined the crystal structure of the complex between furamidine and the DNA dodecamer d(CGCGAATTCGCG)2 and compared it with the same DNA sequence by UV-visible, fluorescence, and CD spectroscopy. Furamidine shows tighter binding to this sequence (Keq = 6.7 x 10(6)) than berenil (Keq = 6.6 x 10(5)). The crystal structure reveals that, unlike berenil, furamidine makes direct hydrogen bond interactions with this DNA sequence through both amidinium groups to O2 atoms of thymine bases and is more isohelical with the minor groove. Molecular mechanics calculations support the hypothesis that these differences result in the improved interaction energy between the ligand and the DNA.

No abstract

The crystal structure of netropsin bound to the decamer d(CGCAATTGCG) has been determined at 2.4 A resolution. This is the first example of a crystal structure of netropsin bound to decamer DNA. The central eight bases of each DNA single-strand base pair with a self-complementary strand to form an octamer B-DNA duplex. These duplexes lie end to end within the unit cell. The terminal 5'-C and G-3' bases are unpaired and interact with the neighboring duplexes via interactions within both the major and minor groove to form base triplet interactions of the type C(+)-G x C and G*(G x C), respectively. The triplet interaction of the type C(+)-G x C is known to exist within triplex DNA with the C+ base oriented parallel with the Watson-Crick guanine base to which it hydrogen bonds. The netropsin molecule lies within the minor groove of the octamer duplex and assumes a class I type position, with bifurcated hydrogen-bonding interactions from the amide groups of the netropsin to the A x T base pairs of the minor groove. The netropsin molecule fits within a five base pair long minor groove site by bending of the flexible amidinium group at one end of the drug.