Mixed sequence DNA can exist in two right-handed and one left-handed double helical conformations--A, B and Z. Under conditions of high water activity the B conformation prevails. If the water activity is reduced on addition of salt or organic solvents, transformation occurs to A-DNA or, in DNAs with alternating purine-pyrimidine sequences, to the left-handed Z-DNA. In crystal structure analyses of oligonucleotides, the free oxygen atoms of adjacent phosphate groups along the polynucleotide chain in B-DNA are found at least 6.6 A apart and individually hydrated whereas they are as close as 5.3 A in A-DNA and 4.4 A in Z-DNA, and bridged by water molecules. We suggest that this more economical hydration in A- and Z-DNA compared with B-DNA is the underlying cause of B----A and B----Z transitions.

Base Sequence↗

PubMedDate not supplied

Unusual photochemical transformation of 5-ethylorotate to 5-ethylidenehydroorotate.

Ultraviolet irradiation of 5-ethylorotate in aqueous medium led to formation of 5-ethylidenehydroorotate via a 1,3-hydrogen rearrangement from the ethylene group of the 5-substituent to the ring C6. The same product was also obtained by an alternate pathway via a hitherto unidentified intermediate. The structure of this unusual pyrimidine analogue, established in the solid state by X-ray diffraction, was shown with the aid of spectroscopic methods to be the same in solution, and some of its properties are described. Heating of 5-ethylidenehydroorotate in the solid state led by direct conversion to a mixture of the parent 5-ethylorotate and 5-ethyluracil. By contrast, ultraviolet irradiation in aqueous medium resulted in quantitative photochemical conversion of the photoproduct to 5-ethyluracil.

Hot Temperature↗

PubMedDate not supplied

The crystal structure of the pyrimidine analogue calcium 5-ethylidenehydroorotate-1.5 hydrate, a photoproduct of ethylorotate.

X-ray diffraction methods have been employed to establish the crystal structure of a new, unusual pyrimidine analogue, 5-ethylidenehydroorotate, obtained by a photochemical rearrangement of 5-ethylorotate. Crystals of the calcium salt of the title compound are monoclinic, space group Pc, cell constants a=14.631, b=10.038, c=19.168 A, beta=137.7 degrees, and contain four molecules, two cations and three water molecules per asymmetric unit. The structure was solved by direct methods and refined to R=5.2% on the basis of 2653 diffractometer measured data. The four independent molecules represent two pairs of enantiomers with slightly differing conformations linked together by an intricate system of hydrogen bonding and Ca2+-coordination (pentagonal bipyrimidal). The structure of the compound in aqueous medium, established by spectral methods, is the same as that in the crystal.

Models, Molecular↗

PubMedDate not supplied

X-ray-diffraction study and determination of absolute configuration of the anticancer drug S(--)cyclophosphamide (Endoxan, Cytoxan, NSC-26271).

(--)Cyclophosphamide(1) crystallized from tetrachloromethane in the triclinic space group P1 with cell dimensions a = 10.500 (4) A, b = 10.490 (4) A, c = 10.761 (4) A, alpha = 110.0 (2) degrees, beta = 110.0 (2) degrees, gamma = 108.9 (2) degrees. Three molecules are contained in the unit cell. The X-ray analysis was based on diffractometer measurement of 2635 independent reflections and the structure was solved by Patterson and direct methods. The final R and Rw factors after full-matrix least-squares refinement are 0.0717 and 0.0677, respectively. The absolute configuration is S based on Hamilton's R-factor ratio test. The oxazaphosphorinane ring exists in a chair form with the bis-beta chloroethyl-amino group in equatorial position and about perpendicular to and bisecting the O--P--N plane. The structure is similar to that found in racemic 1 except a different conformation about one ethyl-amino N--C bond.

Cyclophosphamide↗

PubMedDate not supplied

[Influence of pH, temperature and polarity of the solvent on the absorption of NADH+ and NADH at 260 nm (author's transl)].

Assuming a reversible equilibrium of an unfolded and a base-stacked conformation of both NADH and NAD+ the influence of pH, temperature and methanol on this equilibrium was studied as indicated by the UV-absorption of the adenine, band at 260 nm. By the addition of methanol as well as by an increase of temperature the equilibrium is shifted to the unfolded conformation. An increase of the H+ concentration seems to favor the unfolded conformation in the case of NAD+ while for NADH a decrease of the absorption coefficient is pointing to a higher percentage of the stacked conformation at lower pH. From the temperature variation of the absorption coefficients the enthalpies for the conformational change were calculated and compared with data obtained by different methods.

Hydrogen-Ion Concentration↗

PubMedDate not supplied

M.TaqI: possible catalysis via cation-pi interactions in N-specific DNA methyltransferases.

The adenine-specific DNA methyltransferase M.TaqI transfers a methyl group from S-adenosylmethionine to N6 of the adenine residue in the DNA sequence 5'-TCGA-3'. In the crystal structure of M.TaqI in complex with S-adenosylmethionine the enzyme is folded into two domains: An N-terminal catalytic domain, whose fold is conserved among S-adenosyl-methionine dependent methyltransferases, and a DNA recognition domain which possesses a unique fold. In the active site, two aromatic residues, Tyr 108 and Phe 196, are postulated to bind the flipped-out target DNA adenine which becomes methylated. By lowering the energy of the positively charged transition state via cationic-pi interactions, these two residues probably hold a key role in catalysis.

Adenine↗