Linked Life Data

8755713

Source:http://linkedlifedata.com/resource/pubmed/id/8755713

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
1996-9-16
pubmed:abstractText
We report a comparative spectroscopic study of a novel self-complementary duplex decamer, d(GCGAAT-3'-3'-(alpha T)-5'-5'-CGC)2, in which an alpha-anomeric nucleotide has been inserted into the sequence in a parallel orientation via 3'-3' and 5'-5' phosphodiester bonds, and its unmodified B-DNA analog, d(GCGAATTCGC)2. Plots of the hyperchromicity and circular dichroism of these oligonucleotides are virtually identical, indicating that the overall base stacking and handedness are preserved in the alpha duplex. Thermodynamic parameters extracted from UV melting experiments show that the alpha duplex is only slightly less stable than the control. A near complete set of 1H and 31P nuclear magnetic resonance (NMR) assignments were obtained for both duplexes using classical one- and two-dimensional approaches. Several lines of evidence, in particular, imino 1H, 31P, nuclear Overhauser enhancement, and deoxyribose ring proton spin-spin coupling data, convincingly demonstrate that the overall structural integrity of the alpha and control duplexes are quite comparable, with any perturbations in the former localized to the regions of the construct encompassing the alpha-nucleotide and the unique backbone linkages. Specifically, the alpha duplex exhibits normal Watson-Crick type base pairing, it remains antiparallel except at the inverted nucleotide, all bases are in the anti orientation, and the sugar ring puckering is predominantly "S"-type. However, the J-coupling information for the alpha-nucleotide and the neighboring (3') cytidine are notably different, and reflect a decrease in the amplitude of the sugar pucker in alpha T7, and a significant shift in the conformational equilibrium of the furanose ring in C8 toward the "N"-type pucker. The feasibility of synthesizing oligodeoxynucleotides containing a combination of alpha sugars and short parallel stranded segments, their propensity for forming stable duplexes, and the structural insights into such complexes reported here are of potential importance in the area of antisense therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9355-65
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8755713-Base Composition, pubmed-meshheading:8755713-Base Sequence, pubmed-meshheading:8755713-Circular Dichroism, pubmed-meshheading:8755713-Computer Simulation, pubmed-meshheading:8755713-DNA, pubmed-meshheading:8755713-DNA, Complementary, pubmed-meshheading:8755713-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:8755713-Magnetic Resonance Spectroscopy, pubmed-meshheading:8755713-Models, Molecular, pubmed-meshheading:8755713-Molecular Sequence Data, pubmed-meshheading:8755713-Molecular Structure, pubmed-meshheading:8755713-Nucleic Acid Conformation, pubmed-meshheading:8755713-Oligodeoxyribonucleotides, pubmed-meshheading:8755713-Oligonucleotides, Antisense, pubmed-meshheading:8755713-Phosphoric Acid Esters, pubmed-meshheading:8755713-Software, pubmed-meshheading:8755713-Spectrophotometry, pubmed-meshheading:8755713-Thermodynamics
pubmed:year
1996
pubmed:articleTitle
Structure of a DNA duplex that contains alpha-anomeric nucleotides and 3'-3' and 5'-5' phosphodiester linkages: coexistence of parallel and antiparallel DNA.
pubmed:affiliation
Department of Pharmacology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't