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The NMR solution structure of a 38-nucleotide RNA representing the entire stem-loop D domain with the consensus sequence for enteroviruses and rhinoviruses is investigated. The results also indicate that although the primary sequences of the apical loops in these three RNAs are different, they adopt very similar three-dimensional structures that conform to the previously established UNCG-type tetraloop motif.

Research has been conducted on prion protein. The transformation of the prion protein normal cellular isoform to the infectious prion protein has entailed a metastable locally disordered prion protein conformer, the stability and structural features of this conformer have been characterized via NMR spectroscopy and the results indicate that the conformer coexists in solution.

Nuclear magnetic resonance spectroscopic analysis of the Okazaki fragment containing a single gemcitabine substitution shows alteration in electrostatic properties in terms of the electron density enhancement at the germinal difluoro group. Furthermore, it alters the structural and thermodynamic properties of DNA.

Results demonstrate that in the CAA-TTG sequence region of duplex DNAs, exhibit a slow motion in the microsecond-to millisecond range. The CAA-TTG sequence has a flexible to unstable pyrimidine-purine dinucleotide step in which the purine base is adenine.

A study was conducted to characterize the structure of a homodimer determined by a synthetic 25 residue DNA oligonucleotide which supports single-stranded nucleic acids called a pseudosquare knot (PSQ). Nuclear magnetic resonance was carried out to represent sequences, structures and numbering schemes. Results indicated the frequency of sequences compatibility with PSQ formation in single-stranded genomes.

Research was conducted to determine the three-dimensional structure of d(GCATATGATAG)*d(CTATCATATGC) using two-dimensional nuclear Overhauser effect and double-quantum-filtered COSY spectra. the complete relaxation matrix program MARDIGRAS was ran several times utilizing 2D NOE spectra for exchangeable and nonexchangeable protons at various mixing times. R factors suggest that the structures were in good agreement with the experimental NOE data.

A study was conducted to characterize DNA duplex structures in solution utilizing nuclear magnetic resonance. Motional models have been utilized to determine data for three DNA duplexes while H8-sugar proton distances were correlated with glycosidic torsion angle for adenosine 5. Results indicated that short base-H1' bounds correlated with glycosyl bond motion. Finding also showed that DNAminiCarlo plots supported MD-tar simulation analyses.

Nuclear magnetic resonance spectroscopic study was utilized to describe the solution structure and backbone dynamics of the human alpha3-chain type VI collagen. Results have shown that the global fold configuration retained its form in the solution phase and assumed the same form as in the crystal phase and C5 domain core. It was indicated that the additional six residues in the N-terminal and the 12 residues in the C-terminal affected the function of the C5 domain.

The folding and unfolding of a 142 residue polypeptide with the SHaPrp 27-30 sequence containing all four putative core, alpha-helical segments have been investigated. HPLC, CD, FTIR, analytical sedimentation, mass spectroscopy and NMR were used in the study. The results showed that rPrP could be folded into pH-dependent alpha-helical conformations, a thermodynamically more stable beta-sheet and different stable or transient intermediates.

Two-dimensional nuclear magnetic resonance (NMR) spectroscopy was done on a hybrid nucleic acid duplex formed by methylphosphonate oligodeoxyribonucleotide and its target oligoribonucleotide. The results showed that the hybrid duplex appear to exhibit an overall solution structure which is different from standard B- and A-forms, although the RNA strand demonstrates features of the A-form. It was also indicated that the hybrid duplex appear to have a DNA strand with significant conformational plasticity.

The stereochemistry of base-catalyzed H/D exchange on 13 beta-substituted ethyl butanoates in ethanol-d was investigated to examine the steric and electronic factors which regulate the diastereoselectivity of electrophilic attack on enolate anions. Results indicated that stereoelectronic factors generally produce higher stereoselection than steric effects. Electronegative heteroatom substituents at C-3 resulted in a 10:1 ratio of the 2R*, 3R*/2R*, 3S* 2-deuteriobutanoates.

The authentic Ni(I) complex (Ni(psnet))1+, where psnet = (bis(5-(diphenylphosphino)-3-thiapentanyl)amine), reacts with acids in nonaqueous media to produce dihydrogen (H2). The production of H2 is related to Ni(I) oxidation. Kinetic analysis reveals that the reaction between (Ni(psnet))+ and HCl to form (Ni(psnet)Cl)+ and H2 has two pathways which depend on chloride concentration. A two-term law that includes both the pathways with the protonation of Ni(I) as the initial common step is presented.

Restrained molecular dynamics simulations produced nearly identical results for a R-thiophosphate and S-thiophosphate chirality DNA*RNA hybrid duplex's three-dimensional structures. Time averaged constraints were used during the simulations to explore the hybrids' conformational flexibility and found that pucker transitions between the S and N domains were experienced by the complexes' deoxyriboses moieties.

The synthesis of two redox-active Ni(II) complexes containing hard-soft donor sets in tridentate ligands helps examine the ligand properties promoting stabilization of the multiple metal oxidation states within a single complex. Cyclic voltammetric studies of one Ni complex reveals its ability to undergo one-electron oxidation to Ni(III) species. The second complex generates an electron transfer series with four members that are metal centered and have the oxidation states Ni(O-III). Flexible hard-soft ligands responding to stereo-electronic preferences of the metal stabilize the multiple oxidation states of nickel.

2D-NMR experiments help study the solution structure of thiophosphate-modified DNA RNA hybrid duplex. Relaxation matrix analysis of 2D NOE intensities helps determine the interproton distance constraints and a comparative study between quantitative simulations and experimental COSY crosspeaks helps estimate J-coupling values. Hybrid duplexes are more flexible than DNA or RNA and spectral studies of the two stereoisomers of modified DNA. RNA hybrid duplex reveal different resonances of protons located close to the modified phosphate.

Proton NMR spectroscopic studies on hepatitis B virus direct repeat sequence d(GGCAGAGGTGAAA).d(TTTCACCTCCTGCC) reveal that the sequence consists of the 11-base-pair sequence with an extra genomic base pair and belong to the B-DNA family. Iterative complete relaxation matrix algorithm MARDIGRAS using data from the duplex sequence's 2-dimensional NOE intensities yields an average of 19 distance limitations for each residue's protein exchange rates. Sugar packer and imino exchange rate studies reveal that the sequence has an anomalous configurational region, focussed around the G8-C19 and G7-C20 pair regions.

Tandem use of two-dimensional nuclear Overhauser enhancement (NOE) intensities of the deoxyribose sugar ring and simulations of restrained molecular dynamics help obtain accurate structural information on DNA fragments. Rigidity of NOE data is overcome by enhancing conformational flexibility. Sequence-dependent geometrical structure variations and the bend of the helical axis into the major groove, are observed.

Restrained molecular dynamics measurements and NMR spectroscopy help analyze the three-dimensional solution structure of a tridecamer DNA duplex sequence, present in the conserved domain of HIV-1 genome's long hindermost repeat. The structure is contracted more longitudinally than the classical B-DNA, and many base pairs show considerable propellar twist. Compared to the CTTG-pyr sequence, the - CTTG-pur sequence has a greater roll and slide for the TG step.

A conserved sequence in the long terminal repeat of the HIV genome is identified. This sequence can be used as a pattern in designing drugs that will inhibit transcription and even reverse transcription. Proton nuclear magnetic resonance for the this conserved sequence is assigned using a synthetic DNA duplex. Two-dimensional nuclear Overhauser enhancement and double-quantum-filtered correlation spectral analyses were also employed to determine distance and torsion angle constraints.

A study was conducted to determine the structural parameters of a DNA complex containing the octamer element of immunoglobulin genes. Coupling constants for the deoxyribose protons were extracted and the line widths of terminal nucleotides were observed. Results showed that the deoxyriboses in the DNA fragment were in the form of an equilibrium mixture of at least two conformations. Sugar pucker was also found to depend on pyrimidine and purine bases.

A DNA octamer containing a restriction segment for EcoRI with 5-fluorouracil substituting one thymine nucleotide (GGAATUCC) was analyzed using two-dimensional nuclear Overhauser effect (2D NOE) and double-quantum filtered correlation (2QF COSY) spectra. Results indicate that including computed distances from 2D NOE and torsion angles derived from 2QF-COSY in restrained molecular dynamics calculations is useful in the high resolution determination of the structure of oligonucleotides in solution. Furthermore, a convergence of results was observed when both A-DNA and B-DNA were used. Energy values were likewise correlated with the determined structure.

Determination of biomolecular structure in solution by multidimensional nuclear magnetic resonance and modeling with distance geometry and restrained molecular dynamics (rMD) results in a single structure in accord with structural constraints. The constraints are time-averaged with rapid conformational fluctuations. The ensemble R-factors resulting from MD-tar are the lowest R-values obtained for the octamer, indicating that there is no standard rMD snapshot better than the MD-tar ensemble.

The structure-activity relationship of a newly discovered small molecule, Lys-Ala-7-amido-4-methylcoumarin (KA-AMC), which could promote genomic dimer maturation is reported. The KA-AMC might serve as simplified system for study of nucleocapsid-mediated maturation and might find potential application in structure-based design of inhibitors used for potential HIV therapeutic.

The functions, for which positive-strand RNA viruses in the picornaviridae family utilize their genomic RNAs, are stated. The RNA with the 5'-AUUCCU bulge sequence adopts an overall U shape and its bulge sequence exhibits only limited flexibility.

The critical aspects of the slow fluctuation dynamics of the recombinant hamster prion protein called rPrP, based on nuclear magnetic resonance (NMR) relaxation analysis using Carr-Purcell-Meiboom-Gill (CPMG) experiments, are presented. The result shows that the slow motions in PrP(super c) cellulars are related to the trajectories leading to the transition to PrP(super *).

The identification of the phenothiazines by virtual screening as ligands for TAR RNA and A-site ribosomal's binding in each case is experimented. The scaffold for constructing RNA-binding ligands is served by the phenothiazines.

Research has been conducted on nucleotide RNA hairpin with CACG tetraloop sequence and U.G closing base pair. The authors report the NMR structure of this hairpin which demonstrates that its structure is similar to that of cUNCGg tetraloops.

It is demonstrated that a D2O solution is preferable for saturation transfer difference NMR experiments with small RNA targets due to reduced relaxation rates and the extra spectral window available from ca.6.0-7.3 ppm. The main application for these experiments will be low-throughput screening of focused libraries in drug discovery and optimization.

An analysis of the nonexchangeable proton distances and bounds using a two-dimensional nuclear Overhauser effect (2D NOE) is presented. The 2D NOE spectra which made use of a complete relaxation matrix analysis accounts for the dipole-dipole interactions of proton. In addition, the influence of proton peak exchange on the determination of distances and bounds for protons which exchange with bulk is examined.

The structure of the prion protein rPrP(90-231) of the Syrian hamster is refined using nuclear magnetic resonance. To this end, the structure is refolded to resemble the normal cellular isoform PrP(super C) immunologically and spectroscopically. The refinement is aimed at determining important dynamic and structural properties of the protein which can be linked to biological observations essential to prior diseases. Comparison of the protein structure with previous data reveals sequence-dependent characteristics that may be reflected in a species barrier to the transmission of prion diseases.

The solution structures for the [OKA] and [ARAC] Okazaki fragments, intermediates that form during the lagging strand DNA replication, differ only in the substitution of cytarabine in [ARAC] for one deoxycytidine [OKA]. The solution structures of the fragments each consist of two domains, namely, a DNA duplex region, and an RNA-DNA hybrid duplex region. The helical axes for DDR and HDR of [OKA] are bent 22 degrees relative to one another.