Actinomycin D binds strongly to d(TGTCATTG), a single-stranded DNA devoid of GpC sites

Biochemistry
F M Chen, Feng Sha

Abstract

Despite the absence of the GpC sequence and complete self-complementarity, d(CGTCGTCG) has recently been shown to bind strongly to actinomycin D (ACTD) with a binding density of about one drug molecule per strand. To further elucidate the nature of such a binding, studies are herein made with single-base G --> A and C --> T replacements in d(CGTCGTCG) to identify the DNA bases that play important roles in the strong ACTD binding of this oligomer. On the basis of these results, the octamer d(TGTCATTG) has been identified as a potentially strong ACTD binder. Indeed, binding titration confirms such an expectation and reveals an ACTD binding constant of about 1 x 10(7) M(-1) and a binding density of roughly 0.8 drug molecule per DNA strand for this strong binding mode. Similar binding studies with single-base substitutions on d(TGTCATTG) further reveal the relative importance of the C and G bases on its ACTD binding, with the 3'-terminus G appearing to be the most crucial base. Further base substitutions lead to the conclusion that these C and G bases act in concert rather than individually in the ACTD binding of d(TGTCATTG). Spectral comparisons with the apparently single-stranded GpC-containing d(TGCTTTG) led to the proposal of a...Continue Reading

Citations

Jan 13, 2004·Nucleic Acids Research·Fu-Ming ChenShan-Ho Chou
Jun 8, 2001·Annual Review of Biochemistry·P A Frey
May 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Shan-Ho ChouFu-Ming Chen

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