Biomedical subjects

M M Dhingra

Publications and source records attributed to M M Dhingra.

25 records · Page 2Linked to original sources

PubMed1983

Poly(dA-dT).poly(dA-dT) in low salt appears to be a left-handed B-helix combined use of chemical theory, fiber diffraction and NMR spectroscopy.

Poly(dA-dT).poly(dA-dT) can adopt the B- and D- forms in the fibrous state. Theoretical energy calculations and fiber diffraction analyses suggest that there can be three structural models of poly(dA-dT).poly(dA-dT) in each of these two forms viz right and left-handed Watson Crick models and left-handed Hoogsteen--a total of six possible models. Fiber data for the polymer in the B- or the D-form or energy calculations cannot distinguish any one model from the other. However, a comparison of observed proton chemical shifts with the theoretically computed ones and the NOE studies on exchangeable and nonexchangeable protons suggest that poly(dA-dT).poly(dA-dT) in low salt solution exists predominantly in the left-handed B-conformation.

Base Composition↗

PubMed1983

Determination of handedness of DNA double helices from NOE difference spectra: the structure of poly(dG-dC).poly(dG-dC) in low salt.

Combined use of shielding constant computations, measurements of chemical shifts and NOE studies reveal that poly(dG-dC).(poly)dG-dC) in low salt solutions exist as a right-handed B-DNA double helix described by Gupta, Dhingra, Sarma, Sarma, Rajagopalan and Sasisekharan, J. Biomole. Str. Dyn. 1. 395, 1983. We present a simple and direct method to determine the handedness of DNA double helices from NOE difference spectra. This method takes advantage of the NOE between base protons and the H2'H2" sugar protons; and in the difference NOE spectra in the H2'H2" region the signatures of the right and left-handed helices become imprinted.

DNA↗

PubMed1981

Left handed double helices: effect of sequence on the spatial configuration of high anti nucleic acids.

The conformational properties of purine-pyrimidine and pyrimidine-purine dinucleoside monophosphates in which the glycosidic torsion is fixed to congruent to 120 degree by the formation of a covalent link between the base and the sugar ring are explored by 1H NMR spectroscopy in order to obtain information about the spatial configuration of high anti nucleic acids. The intramolecular stack of the high anti dimers were found to be left handed, in contrast to that (right handed) for natural oligomers, which are low anti. Even though both the high anti pyrimidine-purine and purine-pyrimidine dimers have similar backbone torsion angles, they display widely different relative geometry between the bases; thus in the former there is extensive base-base overlap in the stack, and in the latter there is negligible intramolecular base-base overlap. In addition it was found that purine-pyrimidine systems form miniature double helices in which there is substantial interstrand purine-purine interaction; on the other hand the pyridine-purine high anti dinucleosides have no proclivity to form such base-paired complexes in solution. Mathematical polymerization of the conformation of the high anti purine-pyrimidine dinucleoside monophosphates generates a left handed helix for high anti polynucleotides. This also means that the double helix for high anti-nucleic acids containing purine-pyrimidine repeated units may also be left handed, as had been suggested [Sundaralingam, M., & Yathindra, N. (1977) Int. J. Quantum Chem., Quantum Biol. Symp. 4, 285]. It is suggested that the plasticity in the structure of genomic DNA is such that, if under certain conditions of interactions the sugar-base torsion of certain domains assume high anti values, that domain will become left handed, and this in turn can be a mechanism for the control of expression by genomic DNA.

Dinucleoside Phosphates↗

PubMed1980

Conformational flexibility of the 3' acceptor end of transfer ribonucleic acid.

The intimate details of the conformational features and dynamics of the trinucleoside diphosphates CpCpA and ApCpC in aqueous solution have been arrived at by the complete analysis of their proton magnetic resonance spectra. In addition to the right-handed stacked species in which the phosphodiester torsions conform to the gauche-gauche domains, sugar puckers 3E, C4'-C5 approximately equal to 60 degrees, C5'-O5' approximately 180 degrees, C3'-O3' approximately equal to 205 degrees, and chi CN approximately equal to 40 degrees, the trimers display a variety of spatial configurations, an important one being a bulged configuration in which the central nucleotide unit is bulged out, enabling stacking interactions between the end units. It is further shown that the 3' acceptor end of tRNA, CpCpA, displays considerable flexibility for the terminal adenine nucleotide unit. Theoretical NMR calculations demonstrate that the predominant solution conformation does not conform to the CCA terminus of tRNA as reported by four independent crystallographic studies of tRNAPhe. It is shown that the preferred intramolecular order of CCA in solution is such that chi 1 = chi 2 = chi 3 = 40 degrees, all the three sugars are in 3E, psi 1 = psi 2 = psi 3 = 60 degrees, phi 2 and phi 3 = 170 and 180 degrees, respectively, phi 1 = phi 2' = 205 degrees, and omega 1/omega 1 and omega 2/omega 2' = 240/205 degrees and 295/265 degrees, respectively.

Base Sequence↗

PubMed1978

Stereodynamics of dimer segments of RNA in aqueous solution.

Arguments are presented which show that conformations II and III proposed by Lee and Tinoco [Lee, C.H., and Tinoco, I., Jr. (1977), Biochemistry 16, 5403] for ribodinucleoside monophosphates in aqueous solution are untenable. It has been shown that ribodinucleoside monophosphates exist in aqueous solution as an equilibrium blend of the classically recognized right-handed stack (g-g-), loop stack (g+g+), skewed (g+t), and extended arrays. In order to determine the effect of epsilonA base on the conformer distribution in the equilibrium blend, detailed ring-current calculations were performed and the isoshielding curves for epsilonA were derived. Use of these curves vis-a-vis dimerization shift data indicates that introduction of epsilonA perturbs the equilibrium blend which causes an increase in the population of skewed (g+t) arrays.

Magnetic Resonance Spectroscopy↗

PubMed1978

Why do nucleic acids have 3'5' phosphodiester bonds?

Details of the stereochemistry of the 2'5' and 3'5' dinucleoside monophosphates of polynucleotides have been delineated in aqueous solution using nuclear magnetic resonance spectroscopy. Incorporation of these experimentally determined geometries into the structure of polynucleotides reveals that the intrinsic spatial configurations of the 2'5' bonds cannot support helical structures whereas the geometries of 3'5' bonds allow the formation of helical configurations for RNA.

Magnetic Resonance Spectroscopy↗

PubMed1978

Spatial configuration of deoxyribotrinucleoside diphosphates in aqueous solution.

The detailed conformational features and dynamics of the naturally occurring deoxyribotrinucleoside diphosphates d-TpTpT and d-TpTpC have been investigated at 20 degrees C and 80 degrees C in aqueous solution by nuclear magnetic resonance spectroscopy. The observed NMR parameters indicate that the conformational properties of the trimers are very similar to those of the constituent dimers and monomers, i.e., the monomers and dimers conserve their intrinsic conformational features when they become incorporated into oligomers. Model building indicate that the distant shieldings can originate from spatial configurations in which the central nucleotidyl unit is bulged out and the w'1w1, w'2w2 occupy /g+g+, g+g+/ domains.

Magnetic Resonance Spectroscopy↗