The 3'-N-sulfamate analogue of thymidylyl(3'-5')thymidine (TnsoT, 1) exhibits a preference for a C3'-endo conformation in the solution and solid states. Its photochemical behavior in solution is compared to that of its natural counterpart, thymidylyl(3'-5')thymidine (TpT, 2), to get further insight into the significance of the C3'-endo conformation on the photoproduct formation at the single-stranded dinucleotide level. Irradiation at 254 nm of 1 led to the same type of photoproducts as observed with 2. However, 1 was significantly more photoreactive than 2, and accordingly, the initial rate of photoproduct formation was enhanced in accordance with its propensity to base stack compared to 2. The corresponding quantum yields were determined and showed that the enhancement factor (1 compared to 2) is moderate for the cyclobutane pyrimidine dimer (CPD) (1.26) and much higher for the (6-4) photoproduct (1.8). These data strongly suggest that the CPD and (6-4) photoproduct arise from distinct minor stacked conformations.

The synthesis of a building block containing the photobiologically relevant cis–syn thymine cyclobutane photoproduct and its incorporation into oligonucleotides by the phosphoramidite-based solid-phase synthesis is reported. Compared to previous syntheses, this route is extremely short and allows such modified oligonucleotides to be easily available for biological studies.

Pyrimidine (6-4) pyrimidone photoproducts represent one of the major mutagenic and carcinogenic class of DNA damage produced by UV exposure. At present, besides their conversion to their Dewar valence isomer, (6-4) photoproducts are generally believed to be photostable, and the observed biological properties of Paterno-Büchi-derived photoproducts are, thus far, exclusively attributed to these two types of compounds. Using a model system (2) relevant to DNA photochemistry, we have observed that the 5'-base moiety of the (6-4) thymine dimer 3, under far-UV radiation, is able to undergo a ring contraction leading to a 2-oxoimidazoline, 1. This unprecedented secondary photochemical reaction constitutes the first report of a major photomodification affecting (6-4) photoproducts and strongly questions the biological stability of the (6-4) adducts under UV light with 2-imidazolone (5-4) pyrimidone adducts being possibly another source of endogenous DNA damage.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A T-T dimer characterized by an amide linkage to replace the phosphodiester backbone has been synthesized using a modified radical strategy. The new synthetic approach makes use of a thymidin-3'-yl phosphorodithioate derivative as a precursor of 3'-allyl-3'-deoxythymidine. Standard chemical transformations of this derivative led to the desired T-T dimer incorporating an amide bond. The latter was irradiated with 254 nm wavelength light to yield mainly cyclobutane and [6-4] photoadducts.

A nucleoside dimer in which the natural phosphodiester bond is replaced by an isosteric amide linkage has been prepared. This dimer analogue was subsequently incorporated chemically at the cleavage position of a hammerhead ribozyme substrate. Although the resulting substrate analogue exhibited a high affinity for the ribozyme as shown by gel retardation assays, the amide bond proved to be fully resistant to cleavage under standard conditions of ribozyme cleavage activity.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The binding of Escherichia coli and Lactococcus lactis Fapy-DNA glyosylase (Fpg) proteins to DNA containing either cyclic or non-cyclic abasic (AP) site analogs was investigated by electrophoretic mobility shift assay (EMSA) and by footprinting experiments. We showed that the reduced AP site is the best substrate analog for the E.coli and L.lactis enzymes ( K Dapp = 0.26 and 0.5 nM, respectively) as compared with the other analogs tested in this study ( K Dapp >2.8 nM). The 1,3-propanediol (Pr) residue-containing DNA seems to be the minimal AP site structure allowing a Fpg specific DNA binding, since the ethyleneglycol residue is not specifically bound by these enzymes. The newly described cyclopentanol residue is better recognized than tetrahydrofuran (for the E.coli Fpg, K Dapp = 2.9 and 25 nM, respectively). These results suggest that the hemiacetal form of the AP site is negatively discriminated by the Fpg protein suggesting a hydrogen bond between the C4'-hydroxyl group of the sugar and a Fpg residue. High-resolution hydroxyl radical footprinting using a duplex containing Pr shows that Fpg binds to six nucleotides on the strand containing the AP site and only the base opposite the lesion on the undamaged complementary strand. This comparative study provides new information about the molecular mechanism involved in the Fpg AP lyase activity.

A short synthetic route to an appropriately derivatized carbocyclic analogue of abasic site residues of DNA is proposed.

The readily available bicyclic lactone (−)-1 was transformed into diacetate (−)-2 which served in an expeditious route to (−)-aristeromycin (3a) and (−)-carbodine (3b) in acceptable yields.

A hammerhead ribozyme domain incorporating (-)-carbodine 8a and (-)-aristeromycin 8b at selected positions, manifests increased RNase resistance and exhibits significant catalytic activity.

The readily available bicyclic lactone 1 was resolved by treatment with (S)-O-acetyllactyl chloride to give a separable pair of diastereoisomers (−)-3 and (−)-4 the respective configuration of which was deduced from X-ray crystallography performed on the bromo derivative (−)-5.

Oxidation of phenols by benzeneseleninic acid 2 in methylene dichloride leads to the para-quinones, whereas oxidation by benzeneseleninic anhydride 1 is confirmed to afford the corresponding ortho-quinones. Addition of indole, as a phenylselenium (II) trapping agent, inhibits the formation of phenylselenoquinones in the oxidation with 1 or 2.

Tetravalent morpholino-tellurium derivatives 1 and 6 quickly oxidize hydroquinones to quinones and thiols to disulphide under neutral conditions. Bulky phenol 15 is slowly oxidized by 5 and 6 to the diphenoquinone 16.

Several aryltellurinic acid anhydrides have been compared for their oxidising properties in acetic acid. Very high yields of quinones and disulphides can be obtained under conditions where phenols are not oxidised.

A low mol. wt substance (PM < 2000) with immunosuppressive properties has been extracted from bovine spleen: when injected into mice, previously sensitized to sheep red blood cells, this factor reduced the hemolysin plaque forming capacity of spleen cells of treated animals measured vitro in the Jerne's test.