TY - JOUR
T1 - Synthesis and Characterization of a Set of Four Dodecadeoxyribonucleoside Undecaphosphates Containing O6-Methylguanine opposite Adenine, Cytosine, Guanine, and Thymine
AU - Gaffney, Barbara L.
AU - Marky, Luis A.
AU - Jones, Roger A.
PY - 1984/11
Y1 - 1984/11
N2 - A set of four self-complementary dodecanucleoside undecaphosphates, d[CGNGAATTC(O6Me)GCG],1 where N = A, C, G, or T, has been synthesized by a phosphoramidite procedure. A single large-scale preparation of the nonamer d[DMT-GpApApTpTpCp(O6Me)GpCpG] was divided into four portions for synthesis of the dodecamers. The synthesis, purification (high-performance liquid chromatography), and characterization of each of these molecules are described. Each sequence forms a stable duplex, with a Tm between 19 and 26 °C lower than the Tm of the ‘parent molecule d-(CGCGAATTCGCG). The lowest melting sequence is the N = T molecule; the overall order is N = C > A > G > T. Thus O6-methylation of guanine creates a region of localized instability in DNA regardless of the base opposite the lesion, This instability, which could disrupt some regulatory process or event, may be as significant as or more significant than is the mutation itself to the oncogenic process initiated by alkylating agents.
AB - A set of four self-complementary dodecanucleoside undecaphosphates, d[CGNGAATTC(O6Me)GCG],1 where N = A, C, G, or T, has been synthesized by a phosphoramidite procedure. A single large-scale preparation of the nonamer d[DMT-GpApApTpTpCp(O6Me)GpCpG] was divided into four portions for synthesis of the dodecamers. The synthesis, purification (high-performance liquid chromatography), and characterization of each of these molecules are described. Each sequence forms a stable duplex, with a Tm between 19 and 26 °C lower than the Tm of the ‘parent molecule d-(CGCGAATTCGCG). The lowest melting sequence is the N = T molecule; the overall order is N = C > A > G > T. Thus O6-methylation of guanine creates a region of localized instability in DNA regardless of the base opposite the lesion, This instability, which could disrupt some regulatory process or event, may be as significant as or more significant than is the mutation itself to the oncogenic process initiated by alkylating agents.
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U2 - https://doi.org/10.1021/bi00319a004
DO - https://doi.org/10.1021/bi00319a004
M3 - Article
C2 - 6525333
SN - 0006-2960
VL - 23
SP - 5686
EP - 5691
JO - Biochemistry
JF - Biochemistry
IS - 24
ER -