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Synthesis and characterization of oligonucleotides containing site-specific bulky N2-aralkylated guanines and N6-aralkylated adenines

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Abstract

7-Bromomethylbenz[a]anthracene is a known mutagen and carcinogen. The two major DNA adducts produced by this carcinogen, i.e.,N 2-(benz[a]anthracen-7-ylmethyl)-2′-deoxyguanosine (2, b[a]a2G) andN 6-(benz[a]anthracen-7-ylmethyl)-2′-deoxyadenosine (4, b[a]a6A), as well as the simpler benzylated analogs,N 2-benzyl-2′-deoxyguanosine (1, bn2G) andN 6-benzyl-2′-deoxyadenosine (3, bn6A), were prepared by direct aralkylation of 2′-deoxyguanosine and 2′-deoxyadenosine. To determine the site-specific mutagenicity of these bulky exocyclic aminosubstituted adducts, the suitably protected nucleosides were incorporated into 16-base oligodeoxyribonucleotides in place of a normal guanine or adenine residues which respectively are part of the ATG initiation codon for thelac Z′ α-complementation gene by using anin situ activation approach and automated phosphite triester synthetic methods. The base composition and the incorporation of the bulky adducts into synthetic oligonucleotides were characterized after purification of the modified oligonucleotides by enzymatic digestion and HPLC analysis.

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  1. Room 408, Natural Products Research Institute, Seoul National University, 28 Yeonkun-Dong, Jongno-Ku, 110-460, Seoul, Korea

    Ki-Young Moon Ph. D. & Yeong Shik Kim

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  1. Ki-Young Moon Ph. D.
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Correspondence to Ki-Young Moon Ph. D..

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Moon, KY., Kim, Y.S. Synthesis and characterization of oligonucleotides containing site-specific bulky N2-aralkylated guanines and N6-aralkylated adenines. Arch Pharm Res 23, 139–146 (2000). https://doi.org/10.1007/BF02975502

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  • DOI: https://doi.org/10.1007/BF02975502

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