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Biomedical subjects

C M Nunn

Publications and source records attributed to C M Nunn.

26 records · Page 2Linked to original sources
PubMed1994

Crystal structure of gamma-oxapentamidine complexed with d(CGCGAATTCGCG)2. The effects of drug structural change on DNA minor-groove recognition.

The crystal structure of the complex of gamma-oxapentamidine and the DNA dodecamer d(CGCGAATTCGCG)2 has been determined to a resolution of 0.22 nm and an R factor of 18.9%. The gamma-oxapentamidine ligand interacts with the dodecamer by classic minor groove binding via interactions within the A+T-rich region of the minor groove. A chain of solvent molecules lies along the mouth of the minor groove on the outside of the bound ligand. The structural details of the complex are discussed and compared with the closely analogous complex with pentamidine bound to the same dodecamer [Edwards, K. J., Jenkins, T. C. & Neidle, S. (1992) Biochemistry 31, 7104-7109]. The amidinium groups of the ligand do not hydrogen bond to bases, but are in close contact with O4' sugar ring atoms. This in part explains the reduced DNA binding affinity of this ligand compared to pentamidine.

Antifungal Agents↗
PubMed1993

Crystal structure of d(CGCGAATTCGCG) complexed with propamidine, a short-chain homologue of the drug pentamidine.

The crystal structure of the complex between propamidine and the self-complementary DNA dodecamer d(CGCGAATTCGCG) duplex has been determined to a resolution of 2.1 A and a R-factor of 17.4%. The propamidine binds to the DNA within the minor groove, with specific hydrogen-bonding interactions from the amidinium groups to the bases and sugar groups of the DNA, via a 4-base-pair binding site. A network of water molecules lies over the mouth of the minor groove. The structure provides a rationale for the superior DNA-binding properties of propamidine as compared to pentamidine [cf. Edwards, K. J., Jenkins, T. C. & Neidle, S. (1992) Biochemistry 31, 7104-7109]. This is seen to result from (i) decreased minor groove width at the binding site and (ii) reduced mobility of the bound propamidine molecule.

Base Sequence↗
PubMed1991

DNA-drug interactions. The crystal structures of d(TGTACA) and d(TGATCA) complexed with daunomycin.

The anticancer drug daunomycin has been co-crystallized with the hexanucleotide duplex sequences d(TGTACA) and d(TGATCA) and single crystal X-ray diffraction studies of these two complexes have been carried out. Structure solution of the d(TGTACA) and d(TGATCA) complexes to 1.6 and 1.7 Angstrom resolution, respectively, shows two daunomycin molecules bound to the DNA hexamer. Binding occurs via intercalation of the drug chromophore at the d(TpG) step, and hydrogen bonding interactions involving the drug, DNA and solvent molecules. The daunomycin sugar is located in the minor groove of the DNA hexamer and is stabilized by hydrogen bonds between the amino group of the sugar and functional groups on the floor of the groove. The amino sugar of the d(TGATCA) duplex interacts directly with the DNA sequence, while in the d(TGTACA) duplex, the interaction is via solvent molecules. Two other complexes d(CGTACG)-daunomycin and d(CGATCG)-daunomycin have previously been structurally characterized. Comparison of the four structures with daunomycin bound to the triplet sequences 5'TGT, 5'TGA, 5'CGT and 5'CGA reveals changes in the conformation of both the DNA hexamer and the daunomycin upon complexation, as well as the hydrogen bonding and van der Waals' interactions.

Binding Sites↗
PubMed1988

Carbamazepine vs lithium in the treatment and prophylaxis of mania.

Fifty-four acutely manic patients were allocated to treatment on a double-blind basis with either carbamazepine or lithium carbonate. The short-term effects of treatment were studied over a period of six weeks and the longer term, prophylactic, effects over a period of up to a year. Additional 'rescue' medication was allowed when clinically indicated. There was a high drop-out rate from the trial. Despite this, it appeared that valid comparisons between the two treatments could be made. No statistically significant differences were found, but carbamazepine appeared slightly less effective as a treatment for acute mania and more effective as a prophylactic treatment in this group of patients. Possible predictors of individual responsiveness to each treatment are discussed.

Adolescent↗
PubMed1979

Mixed affective states and the natural history of manic-depressive psychosis.

Since neither the unipolar nor the bipolar theories of manic-depressive psychosis explain all its features, an alternative model was tested. The hypotheses are that mixed affective psychoses represent a superimposition on hypomania of a second type of depression which can sometimes develop from the depressive phase of manic-depressive psychosis, and that schizophrenia occurring in the course of a manic-depressive illness is an alternative to mixed affective psychosis. From an examination of the clinical histories of a random sample of people with bipolar manic-depressive psychosis, evidence was found to support both ideas.

Adult↗