Conformational studies of poly (dA-dT)-poly (dA-dT) and its phosphorothioate analogues
Analogues of poly (dA-dT)-poly (dA-dT) were made with phosphorothioate groups in the DNA backbone. The introduction of phosphorothioate groups into the backbone of poly (dA-dT)-poly (dA-dT) allows one to distinguish the d(ApT) and d(TpA) phosphate resonances in the /sup 31/P NMR spectrum. Upon binding of the steroidal diamine dipyrandenium to poly d(AsT) and poly d(TsA), /sup 31/P NMR shows that it is the d(ApT) phosphodiester bond which is most perturbed. Other work has shown that 2M Cs/sup +/ causes the same /sup 31/P shift. The conformational change induced by both cations probably involves a narrowing of the minor groove. The minor groove of these polymers was investigated using the minor groove binding cation, dipyrandium. It was found that the phosphorothiate polymers have increased charge density in their minor groove as compared to poly (dA-dT)-poly (dA-dT). This is probably due to the lower electronegativity of sulfur as compared to oxygen. Introduction of a phosphorothioate diester at the 5'-purine-pyrimidine-3' step causes a significant lowering of that polymer's melting temperature compared to placement of the phosphorothioate diester at the 5'-pyrimidine-purine-3' step. An explanation of the melting behavior of these polymers was found by considering the effect of sulfur substitution on charge distribution along the minor groove together with ideas on sequence-dependent conformation of base-pair steps derived from x-ray crystal studies.
- Research Organization:
- Brown Univ., Providence, RI (USA)
- OSTI ID:
- 6437149
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
Similar Records
Assignment of phosphorus-31 resonances and correlation of chemical shifts with relative electrostatic potential in nucleic acids
Poly(dA-dT). poly(dA-dT) two-pathway proton exchange mechanism. Effect of general and specific base catalysis on deuteration rates
Related Subjects
OLIGONUCLEOTIDES
CONFORMATIONAL CHANGES
NUCLEAR MAGNETIC RESONANCE
ADENYLIC ACID
DNA
MELTING POINTS
PHOSPHORUS 31
THIOIC ACIDS
THYMIDYLIC ACID
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHOSPHORUS ISOTOPES
PHYSICAL PROPERTIES
RESONANCE
STABLE ISOTOPES
THERMODYNAMIC PROPERTIES
TRANSITION TEMPERATURE
550601* - Medicine- Unsealed Radionuclides in Diagnostics