Synthesis, Properties, and NMR Studies of a C8-Phenylguanine Modified Oligonucleotide that Preferentially Adopts the Z DNA Conformation

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• 作者：Peter M. Gannett ; Sue Heavner ; Jonathan R. Daft ; Kevin H. Shaughnessy ; Jon D. Epperson ; and Nancy L. Greenbaum
• 刊名：Chemical Research in Toxicology
• 出版年：2003
• 出版时间：October 2003
• 年：2003
• 卷：16
• 期：10
• 页码：1385 - 1394
• 全文大小：174K
• 年卷期：v.16,no.10(October 2003)
• ISSN：1520-5010

文摘

Carcinogenic aryl hydrazines produce C8-arylated purine adducts. The effect of these adductson DNA conformation and their role in hydrazine carcinogenesis are unknown. Here, wedescribe a new synthetic route to produce these adducts that is also compatible with thesynthesis of the corresponding phosphoramidites needed for oligonucleotide synthesis. Twooligonucleotides were prepared, an unmodified oligonucleotide, d(^5'CGCGCGCGCG^3'), and aC8-phenylguanine modified oligonucleotide, d(^5'CGCGCG*CGCG^3') (G* = 8-phenylguanine).These oligonucleotides were compared using thermal denaturation, circular dichroism, NMR,and molecular modeling. The phenyl modification destabilizes the B DNA form and stabilizesthe Z DNA form such that the B:Z ratio is near one under physiological conditions. In light ofrecent studies that show a role for Z DNA in gene expression and cell transformation, Z DNAstabilization by C8-arylguanine formation from aryl hydrazines may be relevant to their rolein carcinogenesis.