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The structure of homo-DNA duplex [[dd(CGAATTCG)].sub.2] (dd =2',3'-dideoxy-[beta]-D-glucopyranose sugars) is described. It exposes a weakly twisted right-handed duplex with a strong leaning between the hexose-phosphate backbones and base-pair axes, and highly unbalanced values for helical rise and twist at individual base steps.

2'-Deoxy-2'-fluoro-arabinonucleic acid (FANA) and arabinonucleic acid (ANA) paired to RNA are substrates of RNase H. The structural data provide insight into the structural requirements at the catalytic site of RNase H and it is concluded that the relative importance of stereoelectronic effects and hydration as modulators of RNA affinity.

The structural properties underpinning the differences in the immediate environment of a N(super 3)T-ethyl-N(super 3)T interstrand cross link that is inserted into a scaffold wherein the cross link is mispair-aligned is described. Results demonstrate that the lesion defined by mismatch-aligned minor groove N(super 3)T-ethyl-N(super 3)T cross-linked thymine bases produces very localized distortions in a DNA stem that may be difficult to recognize by repair mechanisms that are not transcription-or-replication-coupled.

A cross-link that bridges the N(super 3) positions of a mismatched thymide base pair is synthesized, as a part of the studies on DNA duplexes that contain alkyl interstrand cross-links. Fully cross-linked duplexes were synthesized using an orthogonal approach to selectively remove protecting groups that allowed construction of the cross-linked duplex via conventional solid-phase oligonucleotide synthesis.

The stability of phosphoroselenoates against oxidation on a crystallographic time scale is studied in comparison with selenium-assisted nucleic acid crystallography. Its role in MAD structure determination is examined.

TNA ((L)-alpha-Threofuranosyl-(3'->2') oligonucleotides) is derived from a sugar containing only four carbon atoms and is one of the simplest potentially natural nucleic acid alternatives investigated in the context of a chemical etiology of nucleic acid structure. Detailed insight into the conformational features of TNA in a double-helical environment is provided.

Results indicate that bending deformations in the helix involving the -CNG- sequence cross-linked DNA duplexes may be controlled by varying the cross-link length. Data show that the cross-link containing 2,4,or 7 methylene groups joins the C residues of a -CNG- sequence in the DnA duplex.

Research has been conducted on the phosphorthioate deoxyribonucleotides used as antisense inhibitors. Results indicate that antisense-directed RNase H degradation of the target RNA is a determinant for the gene-specific antisense oligonucleotide inhibitory potency.

This articles describes the synthesis of N(sup)4C--ethyl--N(sup)4C interstrand cross-linked DNA duplexes employing N(sup)4C--ethyl--N(sup)4C phosphoramidite reagent. The ligated oligomers containing staggered cross-links exhibit differences in structure and stability with -GC- staggered cross-links disrupt hydrogen bonding and affecting helix stability by perturbing adjacent base pairs.

Oligonucleotide hairpins were investigated to determine solution structure and implications for RNase H specificity to DNA/RNA hybrid duplexes.

Research has been conducted on the arabinonucleic acid (ANA) which is the 2'-epimer of RNA. The synthesis of the ANA from the arabinonucleoside building blocks is described.

The DNA repair protein O6‐alkylguanine‐DNA alkyltransferase (AGT), found in numerous organisms, can remove methyl groups from the O6‐ and O4‐atoms of 2′‐deoxyguanosine and thymidine in DNA. AGT variants demonstrate different repair efficiencies towards these lesions. To understand the influence of C5 nucleobase substituents on O4‐methyl removal by AGTs, DNA duplexes containing 5‐chloro‐, 5‐bromo‐ 5‐iodo‐ and 5‐trifluoromethyl‐O4‐methyl‐2′‐deoxyuridine were studied. UV thermal denaturation revealed a stability reduction of 11 °C for the O4‐methyl halogen series and 5‐trifluoromethyl analog relative to their controls. For the 5‐chloro analog efficient repair was observed by human and E.coli AGTs. For the larger halogens (5‐bromo and 5‐iodo) and 5‐trifluoromethyl analog, human AGT showed moderate repair of the O4‐methyl adduct. E.coli OGT and Ada‐C readily repaired most adducts with reduced efficiency for the larger groups, except C5‐iodo. These results suggest electronic contributions and favourable interactions of the C5‐halogens within the AGT active site contribute to efficient dealkylation. [ABSTRACT FROM AUTHOR]

Tetrahedron DNA structures were formed by the assembly of three‐way junction (TWJ) oligonucleotides containing O6‐2′‐deoxyguanosine‐alkylene‐O6‐2′‐deoxyguanosine (butylene and heptylene linked) intrastrand cross‐links (IaCLs) lacking a phosphodiester group between the 2′‐deoxyribose residues. The DNA tetrahedra containing TWJs were shown to undergo an unhooking reaction by the human DNA repair protein O6‐alkylguanine DNA alkyltransferase (hAGT) resulting in structure disassembly. The unhooking reaction of hAGT towards the DNA tetrahedra was observed to be moderate to virtually complete depending on the protein equivalents. DNA tetrahedron structures have been explored as drug delivery platforms that release their payload in response to triggers, such as light, chemical agents or hybridization of release strands. The dismantling of DNA tetrahedron structures by a DNA repair protein contributes to the armamentarium of approaches for drug release employing DNA nanostructures. [ABSTRACT FROM AUTHOR]

A study was conducted to understand the cross-link structure of DNA interstrand that affects the repair in nonreplicating reporter plasmids that contain a mispaired [N.sup.4]C-ethyl-[N.sup.4]C (C-C), N3T-ethyl-N3T (T-T), or N1I-ethyl-N3T (I-T) ICL. The insertion of both, C and G residues at the C-C cross-link site without any need for Rev1 for repair indicated that replicative or other translesion polymerases could bypass the C-C remnant.

The ability of [O.sup.6]-alkylguanine-DNA alkyltransferase to repair interstrand cross-link DNA damage is investigated. The butane cross-links present in the oligodeoxiribonucleotides of DNA are found to hinder the repair mechanism.

Five different amide-linked dimers including structures with homochiral linkers of the type X3'-C*H(CH3)-CO-NH-CH2 (X=O, CH2) as well as the corresponding analogues carrying methoxy groups at the 2'-position of the 3'-nucleoside were synthesized to analyze the influence of various chemistries of such five-atom linkers on the RNA-binding affinity. It was found that some of the five-atom-linked dimers lead to significantly higher RNA-binding affinities compared with that of native DNA.

A study characterizes the repair, structure, and flexibility of DNA that contains N4C-ethyl-N4C interstand DNA cross-link in two different orientations. A combination of (super 1)H nuclear magnetic resonance (NMR), restrained molecular dynamics simulations, and atomic force microscopy (AFM) was used to examine the structure and flexibility of DNA containing these cross-links.

The synthesis of oligonucleotides containing selenium at the 2'-alpha position of uridine and crystallization and structural studies of the selenium containing oligodeoxyribonucleotides is detailed. The 2'-alpha-position selenium derivatization retains the native C3'-endo conformation of A-form DNA and RNA molecules.