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Biomedical subjects

S Neidle

Publications and source records attributed to S Neidle.

At least 163 records · Page 9Linked to original sources
PubMed1983

Monte Carlo studies on water in the dCpG/proflavin crystal hydrate.

The extensive water network identified in the crystallographic studies of the dCpG/Proflavin hydrate by Neidle, Berman and Shieh (Nature 288, 129, 1980) forms an ideal test case for a) assessing the accuracy of theoretical calculations on nucleic acid--water systems based on statistical thermodynamic computer simulation, and b) the possible use of computer simulation in predicting the water positions in crystal hydrates for use in the further refinement and interpretation of diffraction data. Monte Carlo studies have been carried out on water molecules in the unit cell of dCpG/proflavin, with the nucleic acid complex fixed and the condensed phase environment of the system treated by means of periodic boundary conditions. Intermolecular interactions are described by potential functions representative of quantum mechanical calculations developed by Clementi and coworkers, and widely used in recent studies of the aqueous hydration of various forms of DNA fragments. The results are analyzed in terms of hydrogen bond topology, hydrogen bond distances and energies, mean water positions, and water crystal probability density maps. Detailed comparison of calculated and experimentally observed results are given, and the sensitivity of results to choice of potential is determined by comparison with simulation results based on a set of empirical potentials.

Acridines↗
PubMed1983

Computer modelling studies of the covalent interactions between DNA and the enantiomers of anti-7,8-diol,9,10-epoxy-benzo[a]pyrene.

The molecular structures of adducts between the + and - enantiomers of 7,8-diol 9,10-epoxy benzo[a]pyrene and a double-stranded model for DNA, have been examined by empirical energy calculations. Low-energy structures were only obtained for A form, and not B form DNA. Both + and - adducts are of approximately equal energy. Some structural differences in the orientation of the BP chromophore in the two adducts were found.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1983

Molecular modelling studies on the non-covalent intercalative interactions between DNA and the enantiomers of anti-benzo[a]pyrene 7,8-diol-9,10-epoxide.

The non-covalent intercalative interactions between a deoxydinucleoside model for DNA and the enantiomers of anti-benzo[a]pyrene diol-epoxide, have been studied by molecular mechanics and computer graphics methods. Stereoselective differences between major and minor groove sites, and between the enantiomers have been found in terms of attractive close contacts.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1983

X-ray crystallographic analysis of (+/-)-7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene: molecular structure of a 'syn' diol epoxide.

X-ray crystallographic analysis has been used to define the molecular structure of the cis (syn) diol epoxide, (+/-)-7 beta,8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. The two hydroxyl groups are oriented equatorially to the tetrahydrobenzene ring, contrary to predictions and there is no intramolecular hydrogen bonding in the structure.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1982

X-ray crystallographic analysis of 3-(2'-phenyl-2,4'-bithiazole-4-carboxamido) propyldimethylsulphonium iodide, an analogue of the DNA-binding portion of bleomycin A2.

The crystal and molecular structure of the title compound, an analogue of the DNA binding region of bleomycin A2, has been determined by X-ray crystallography. All the three independent molecules in an asymmetric unit are approximately planar with fully extended side chains. A computer graphics model-building study has shown that the phenyl group and the second thiazole ring can be intercalated between the base pairs of the double-stranded deoxydinucleoside phosphate d(CpG), and also that the sulphonium cation can interact with a backbone phosphate group. This model is in accord with NMR spectral data.

Bleomycin↗
PubMed1982

Molecular structure of (+/-)-7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene determined by x-ray crystallography.

The molecular structure of a tetrahydrotetrol that is formed by hydrolysis of (+/-)-7 alpha, 8 beta-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, has been determined by X-ray crystallographic methods. The relative orientations of the four hydroxyl groups of the racemic tetrahydrotetrol (7 alpha, 8 beta, 9 beta, 10 alpha) indicate that the tetrahydrotetrol was formed by the trans opening of the epoxide ring of the diol-oxide. The hydroxyl groups at positions 7 and 8 adopt a diequatorial conformation, while those at positions 9 and 10 adopt a diaxial conformation. Several other geometric features are discussed.

Benzopyrenes↗
PubMed1981

The molecular structure of (+/-)- 7 alpha, 8 beta-dihydroxy-7,8-dihydrobenzo[a]pyrene, an early metabolite of benzo[a]pyrene.

The molecular structure of (+/-)-7 alpha, 8 beta-dihydroxy-7,8-dihydrobenzo[a]pyrene has been determined by X-ray crystallographic methods. The analysis has shown that the two hydroxyl groups are trans to each other and di-equatorial to the ring. The dihydrobenzene group adopts a distorted half-chair pucker. Trends in several bond distances indicate reactive points in the molecule.

Benzopyrenes↗
PubMed1981

Molecular structures of three hydroxyl derivatives of the hepatic carcinogen acetylaminofluorene. Evidence for preferred orientation of the acetylamino side-chain.

The molecular and crystal structures of three hydroxyl derivatives of 2-acetylaminofluorene (AAF), have been determined by X-ray crystallographic analysis. The structures of l-hydroxyl-AAF, N-hydroxyl-AAF and 3-hydroxyl-AAF have shown that in general their geometries are similar, both in respect bond distances and angles, and in respect of side-chain disposition. Possible reasons for the differences in biological activity between the three derivatives are discussed.

2-Acetylaminofluorene↗
PubMed1980

Highly structured water network in crystals of a deoxydinucleoside---drug complex.

X-ray diffraction analysis of crystals of the intercalative complex between the deoxyribonucleoside phosphate d(CpG) and the mutagen proflavine shows a highly structured arrangement of water molecules linked together by newtworks of hydrogen bonds to form four edge-linked pentagons per asymmetric unit. These pentagons have a general role in maximizing hydrogen bonding at 3.4-A intervals. The conformation of the deoxyribose sugar ring at the 3' end of one strand can depend on its local aqueous environment.

Acridines↗
PubMed1980

The structure of drug-deoxydinucleoside phosphate complex; generalized conformational behavior of intercalation complexes with RNA and DNA fragments.

A 2:2 complex of proflavine and deoxycytidylyl-3', 5'-guanosine has been crystallized and its structure determined by x-ray crystallography. The two dinucleoside phosphate strands form self complementary duplexes with Watson Crick hydrogen bonds. One proflavin is asymmetrically intercalated between the base pairs and the other is stacked above them. The conformations of the nucleotides are unusual in that one strand has C3',C2'endomixed sugar puckering and the other has C3',C3' endo deoxyribose sugars. These results show that the conformation of the 3'sugar is of secondary importance to the intercalated geometry.

Acridines↗
PubMed1979

9-beta-D-Arabinofuranosyl-8-n-butylaminoadenine, a C-8 substituted nucleoside in the anti conformation. Crystallographic and NMR studies.

The protein NMR spectrum of 9-beta-D-arabinofuranosyl-8-n-butylaminoadenine shows an unusually low-field 5'-hydroxyl proton resonance, which has been interpreted in terms of an anti glycosidic conformation together with an 05' ... N8 intramolecular hydrogen bond. Confirmatory evidence for this was obtained by an X-ray crystallographic study; in the crystal, the glycosidic angle chi is 52.7 degrees and the sugar pucker is C3' endo-C4' exo.

Butylamines↗