Syntheses and properties of adenine and thymine nucleoside alkyl phosphotriesters, the neutral analogs of dinucleoside monophosphates

Paul S. Miller, Kai N. Fang, Norman S. Kondo, Paul O P Ts'o

Research output: Contribution to journalArticle

Abstract

The methyl and ethyl phosphotriester derivatives of TpT and dApdA were synthesized and were obtained as a pair of diastereoisomers in each case. As shown by pmr, CD, and uv hypochromicity measurements, the conformations of the triesters in solution are quite similar to those of the parent diesters, although there is less base stacking in the triesters. The phosphate-alkyl groups serve as monitors for the interaction between the backbone and the bases. The pmr resonances of these groups provide valuable information about the dynamics of the dimer conformations. Thermal perturbation or denaturation by DMSO causes a loss of the stacked conformation and an overall rotation of the base planes about the C-O-P bonds of the pentose-phosphate backbone. The triesters of dApdA form complexes with poly(uridylic acid) in 0.01 M Mg2+ with a stoichiometry of 2U:1A. The parent diester, dApdA, forms a complex with identical stoichiometry and the secondary structures of all three complexes appear to be the same. The thermal stabilities of the 2 poly(U)-triester complexes are greater than that of the 2 poly(U)-dApdA complex due to decreased repulsion between the negatively charged phosphates of the poly(U) and the neutral phosphotriester backbone. The phosphotriesters are stable in neutral aqueous solutions and are resistant to hydrolysis by snake venom and spleen phosphodiesterase, and by micrococcal nuclease.

Original languageEnglish (US)
Pages (from-to)6657-6665
Number of pages9
JournalJournal of the American Chemical Society
Volume93
Issue number24
StatePublished - 1971

Fingerprint

Dinucleoside Phosphates
Thymine
Adenine
Poly U
Nucleosides
Conformations
Phosphates
Stoichiometry
spleen exonuclease
Denaturation
Hot Temperature
Uridine Monophosphate
Micrococcal Nuclease
Pentoses
Dimers
Hydrolysis
Thermodynamic stability
Dimethyl Sulfoxide
Derivatives
Acids

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Syntheses and properties of adenine and thymine nucleoside alkyl phosphotriesters, the neutral analogs of dinucleoside monophosphates. / Miller, Paul S.; Fang, Kai N.; Kondo, Norman S.; Ts'o, Paul O P.

In: Journal of the American Chemical Society, Vol. 93, No. 24, 1971, p. 6657-6665.

Research output: Contribution to journalArticle

Miller, Paul S. ; Fang, Kai N. ; Kondo, Norman S. ; Ts'o, Paul O P. / Syntheses and properties of adenine and thymine nucleoside alkyl phosphotriesters, the neutral analogs of dinucleoside monophosphates. In: Journal of the American Chemical Society. 1971 ; Vol. 93, No. 24. pp. 6657-6665.
@article{00aa5fd74fcc4ce286e9969205b6df33,
title = "Syntheses and properties of adenine and thymine nucleoside alkyl phosphotriesters, the neutral analogs of dinucleoside monophosphates",
abstract = "The methyl and ethyl phosphotriester derivatives of TpT and dApdA were synthesized and were obtained as a pair of diastereoisomers in each case. As shown by pmr, CD, and uv hypochromicity measurements, the conformations of the triesters in solution are quite similar to those of the parent diesters, although there is less base stacking in the triesters. The phosphate-alkyl groups serve as monitors for the interaction between the backbone and the bases. The pmr resonances of these groups provide valuable information about the dynamics of the dimer conformations. Thermal perturbation or denaturation by DMSO causes a loss of the stacked conformation and an overall rotation of the base planes about the C-O-P bonds of the pentose-phosphate backbone. The triesters of dApdA form complexes with poly(uridylic acid) in 0.01 M Mg2+ with a stoichiometry of 2U:1A. The parent diester, dApdA, forms a complex with identical stoichiometry and the secondary structures of all three complexes appear to be the same. The thermal stabilities of the 2 poly(U)-triester complexes are greater than that of the 2 poly(U)-dApdA complex due to decreased repulsion between the negatively charged phosphates of the poly(U) and the neutral phosphotriester backbone. The phosphotriesters are stable in neutral aqueous solutions and are resistant to hydrolysis by snake venom and spleen phosphodiesterase, and by micrococcal nuclease.",
author = "Miller, {Paul S.} and Fang, {Kai N.} and Kondo, {Norman S.} and Ts'o, {Paul O P}",
year = "1971",
language = "English (US)",
volume = "93",
pages = "6657--6665",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "24",

}

TY - JOUR

T1 - Syntheses and properties of adenine and thymine nucleoside alkyl phosphotriesters, the neutral analogs of dinucleoside monophosphates

AU - Miller, Paul S.

AU - Fang, Kai N.

AU - Kondo, Norman S.

AU - Ts'o, Paul O P

PY - 1971

Y1 - 1971

N2 - The methyl and ethyl phosphotriester derivatives of TpT and dApdA were synthesized and were obtained as a pair of diastereoisomers in each case. As shown by pmr, CD, and uv hypochromicity measurements, the conformations of the triesters in solution are quite similar to those of the parent diesters, although there is less base stacking in the triesters. The phosphate-alkyl groups serve as monitors for the interaction between the backbone and the bases. The pmr resonances of these groups provide valuable information about the dynamics of the dimer conformations. Thermal perturbation or denaturation by DMSO causes a loss of the stacked conformation and an overall rotation of the base planes about the C-O-P bonds of the pentose-phosphate backbone. The triesters of dApdA form complexes with poly(uridylic acid) in 0.01 M Mg2+ with a stoichiometry of 2U:1A. The parent diester, dApdA, forms a complex with identical stoichiometry and the secondary structures of all three complexes appear to be the same. The thermal stabilities of the 2 poly(U)-triester complexes are greater than that of the 2 poly(U)-dApdA complex due to decreased repulsion between the negatively charged phosphates of the poly(U) and the neutral phosphotriester backbone. The phosphotriesters are stable in neutral aqueous solutions and are resistant to hydrolysis by snake venom and spleen phosphodiesterase, and by micrococcal nuclease.

AB - The methyl and ethyl phosphotriester derivatives of TpT and dApdA were synthesized and were obtained as a pair of diastereoisomers in each case. As shown by pmr, CD, and uv hypochromicity measurements, the conformations of the triesters in solution are quite similar to those of the parent diesters, although there is less base stacking in the triesters. The phosphate-alkyl groups serve as monitors for the interaction between the backbone and the bases. The pmr resonances of these groups provide valuable information about the dynamics of the dimer conformations. Thermal perturbation or denaturation by DMSO causes a loss of the stacked conformation and an overall rotation of the base planes about the C-O-P bonds of the pentose-phosphate backbone. The triesters of dApdA form complexes with poly(uridylic acid) in 0.01 M Mg2+ with a stoichiometry of 2U:1A. The parent diester, dApdA, forms a complex with identical stoichiometry and the secondary structures of all three complexes appear to be the same. The thermal stabilities of the 2 poly(U)-triester complexes are greater than that of the 2 poly(U)-dApdA complex due to decreased repulsion between the negatively charged phosphates of the poly(U) and the neutral phosphotriester backbone. The phosphotriesters are stable in neutral aqueous solutions and are resistant to hydrolysis by snake venom and spleen phosphodiesterase, and by micrococcal nuclease.

UR - http://www.scopus.com/inward/record.url?scp=0015168319&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0015168319&partnerID=8YFLogxK

M3 - Article

C2 - 5122782

AN - SCOPUS:0015168319

VL - 93

SP - 6657

EP - 6665

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 24

ER -