S. Neidle

Nucleic acid binding drugs. Part IV. The crystal structure of the anti-cancer agent daunomycin

The crystal structure has been determined of the anti-cancer drug daunomycin, as the hydrochloride monohydrate pyridine salt. The overall structure, previously determined by X-ray analysis of an N-bromoacetyl derivative (Anguili, R., Foresti, E., Riva Di Sanserverino, L., Isaacs, N.W., Kennard, O., Motherwell, W.D.S., Wampler, D.L. and Arcamone, F. (1971) Nat. New Biol. 234, 78-80) has been confirmed, although substantial conformational differences are observed. The conformation described here is very similar to that found for the related drug carminomycin I (Wani, M.C., Taylor, H.L., Wall, M.E., McPhaill, A.T. and Onan, K.D. (1975) J. Am. Chem. Soc. 97, 5955-5956; Pettit, G.R., Einck, J.J., Herald, C.L., Ode, R.H. Von Dreele, R.B., Brown, P., Brazhnikova, M.G. and Gause, G.F. (1975) J. Am. Chem. Soc. 97, 7387-7388); it is suggested that this represents a significantly stable molecular conformation; an intramolecular C(7)...O(9) hydrogen bond is invoked to account for this. This conformation is likely to be at least close to that of daunomycin when bound to DNA.

The crystal and molecular structure of an osmium bispyridine adduct of thymine.

The bispyridine osmium adduct of thymine has been crystallised and subjected to an X-ray diffraction analysis. It crystallises in the triclinic space group P1, with cell dimensions a equals 7.975(3), b equals 10.381(3), c equals 11.036(3) A, alpha equals 82.73(2)degrees, beta equals 77.22(3) degrees, gamma equals 101.75(3), and with two molecules in the unit cell. The analysis has shown that the osmium reagent has added cis across the 5,6 thymine bond.

Nucleic acid binding drugs. VII. Molecular-mechanics studies on the conformational properties of the anti-cancer drug daunomycin: some observations on the use of differing potential-energy functions

The conformation of the anti-cancer drug daunomycin nhas been investigated in detail by potential-energy ncalculations. The flexibility around the ether linkage, nconnecting the anthracycline chromophore and the namino sugar group, has been evaluated using several ntypes of potential-energy function. The results largely nsupport the hypothesis that the crystallographically nobserved conformation is the most stable one, although nconsiderable detailed variation with respect to potential nfunction was found.

The structure of the ribodinucleoside monophosphate guanylyl-3',5'-cytidine as its ammonium octahydrate salt

The crystal and molecular structure of an ammonium octahydrate salt of the ribodinucleoside monophos-phate guanylyl-3,5-cytidine (CIgH24NsOI2P) has been determined by X-ray methods, and refined to a final R of 0.111 for 1197 observed reflections. The salt crystallizes in space group C2 with cell dimensions a -- 20.987 (6), b = 16.470 (4), c = 9.566 (1) fit and fl = 94.36 (2)°; Z = 4 for a calculated density of 1.50 Mg m -3 and #(Cu Ka) = 1.19 mm -1. The unit-cell dimensions are very similar to those of the sodium salt [Rosenberg, Seeman, Day & Rich (1976). J. Mol. Biol. 104, 145-167]; however, the two structures are non-isomorphous. Conformational features of the ammonium salt are as expected for an RNA-like Watson-Crick base-paired duplex.

The structure of Miracil D, a DNA-binding drug.

The crystal structure of the drug Miracil D has been determined. Although the accuracy of the analysis is limited by disorder, it is apparent that the thioxanthone ring system is planar. The proximal nitrogen atom of the side-chain probably forms an intramolecular hydrogen bond with the carbonyl oxygen. The rest of the side-chain has a large degree of conformational mobility.

Drug Nucleic Acid Interactions: Proflavine Intercalation into Double-Helical Fragments of RNA and DNA

The results of crystallographic studies on proflavine complexed with three different dinucleoside phosphate systems, are discussed in terms of backbone and sugar conformations. Extent of drug-base-pair stacking and base-pair mutual orientations are compared and contrasted.

The structure of 1-(16-hydroxy-phenoxymethyl)-3,4-dihydroisoquinoline hydrochloride monohydrate, a topical anti-viral agent

The crystal and molecular structure of the anti-viral agent 1-(16-hydroxy-phenoxymethyl)-3,4-dihydroisoquinoline hydrochloride monohydrate, has been determined by single-crystal X-ray diffraction analysis. A prediction, that the conformation about the C1ue5f8C11 bond should be cisoid, has been confirmed.