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Biomedical subjects

C Altona

Publications and source records attributed to C Altona.

83 records · Page 5Linked to original sources

Loopstructures in synthetic oligodeoxynucleotides.

A comparative nuclear magnetic resonance study of the hydrogen-bonded imino protons in a series of synthetic DNA fragments is presented. The fragments ATCCTA(Tn)TAGGAT are in principle capable of forming either a self-complementary hairpin loop structure (monomer form) or an interior loop structure (dimeric form). It has been shown, that for n = 1 only the dimer structure is present in aqueous solution, whereas the exclusive existence of the hairpin loop structure is indicated for n = 3, 4 & 5. Surprisingly, for n = 2 two different structures appear to be present in solution. Concentration studies show that both monomers and dimers exist side by side in this case. Hairpins as well as interior loops form extra "melting sites" in addition to the wellknown fraying phenomenon at the terminus of the double helix.

Base Composition↗

Conformational characteristics of the trinucleoside diphosphate dApdApdA and its constituents from nuclear magnetic resonance and circular dichroism studies. Extrapolation to the stacked conformers.

Proton NMR studies at 360 MHz were carried out on the trinucleoside diphosphate dApdApdA, the dinucleoside monophosphate dApdA and the methylphosphate esters of the monomers pdA, pdAp and dAp. The compounds were also investigated by means of circular dichroism at varying temperatures. Complete NMR spectral assignments are given. The thermodynamics of stacking derived from the circular dichroic spectra was used to extrapolate the observed coupling constants, measured at a range of temperatures, to values appropriate to the pure stacked states of the dimer and the trimer. The data were interpreted in terms of the N and S deoxyribose pseudorotational ranges [Altona, C. and Sundaralingam, M. (1972) J. Am. Chem. Soc. 94, 8205--8212] and it is shown that the right-handed single helix of the trimer occurs in two distinct forms: the major one corresponds to a B-DNA-like structure, S-S-S; the minor one (30%) has the sugar rings in a hitherto unsuspected S-S-N conformational sequence. The dimer behaves quite similarly, a mixture of 70% S-S and 30% S-N stacks being indicated. The detailed geometry of teh S-type sugar rings is not invariable but appears to undergo a slight shift when another base stacks on top of a given nucleotide unit. The backbone angles of the fully stacked B-DNA-like single helix in solution are (starting the notation at P) beta = 187 degrees, gamma = 50 degrees, delta = 138 degrees, epsilon = 186 degrees.

Circular Dichroism↗

Circular dichroism studies of 6-N-methylated adenylyladenosine and adenylyluridine and their parent compounds. Thermodynamics of stacking.

The temperature dependence of the circular dichroism spectra of two adenylyladenosine and three adenylyluridine dinucleotides in aqueous solution have been studied. The effect of methylation of the N-6 position of the adenylyl moieties on the thermodynamic parameters of the stacking equilibrium was investigated applying a two-state model for the thermodynamic analysis of the experimental data. It is shown that the methylated compounds allow a more accurate analysis of the data and that methylation stabilizes the stacking interaction by a relative decrease of the entropy of unstacking.

Adenosine Monophosphate↗

A conformational study of nucleic acid phosphate ester bonds using phosphorus-31 nuclear magnetic resonance.

A systematic phosphorus-31 nuclear magnetic resonance study of some nucleic acid constituents (6-N-(dimethyl)adenylyl-(3',5')-uridine and some nucleotide methyl esters) is presented. The temperature dependent phosphorus-31 chemical shifts were analyzed by standard thermodynamic procedures. It is shown that gt conformations about the P-O ester bonds have a lower free energy content relative to gg conformers.

Adenosine Monophosphate↗

Conformational analysis of a DNA triplet in aqueous solution. Thymidylyl-(3'-5')-thymidylyl-(3'-5')-2'-deoxyadenosine, d(T-T-A), studied by 1H nuclear magnetic resonance at 360 MHz.

The proton signals of a 50 mM solution of thymidylyl-(3'-5')-thymidylyl-(3'-5')-2'-deoxyadenosine, d(T-T-A), in 2H2O at 65 degrees C and p2H=7.4, were detected by nuclear magnetic resonance at 360 MHz. Complete assignment of the 21 ribose proton signals was achieved by extensive decoupling experiments and computer simulations. The coupling constant data show that the ribose rings prefer to adopt the S (2'-endo) conformation. The presence of a substantial amount of a right handed helical structure of the d(-T-A) fragment is indicated from chemical shift considerations. The molecule displays a high degree of conformational purity along the sugar-phosphate backbone.

DNA↗