Sequence selectivity of DNA alkylation by adozelesin and carzelesin.
Adozelesin and carzelesin are synthetic analogues of the extremely potent antitumor antibiotic CC-1065, which alkylates N3 of adenine in a consensus sequence 5'-(A/T)(A/T)A* (A* is the site of alkylation). We have investigated the DNA sequence selectivity of adozelesin and carzelesin by thermally induced DNA strand cleavage assay using radiolabeled restriction DNA fragments. An analysis of alkylation patterns shows that the consensus sequences for carzelesin and adozelesin have been found to be 5'-(A/T)(A/T)A* and 5'-(A/T)(G/C)(A/T)A*. A new consensus sequence, 5'-(A/T)(A/T)CA*, has been observed to display an additional alkylation site for adozelesin but not for carzelesin. These results indicate that the pattern of sequence selectivity induced by carzelesin is similar but not identical to those induced by adozelesin.
Yoon
J H
JH
Department of Biochemistry, College of Natural Sciences, Yeungnam University, Kyongsan, Korea.
Lee
C S
CS
D000225:Adenine / Q000378:metabolism; D000478:Alkylation; D000970:Antineoplastic Agents / Q000378:metabolism*; D001483:Base Sequence; D001572:Benzofurans / Q000378:metabolism*; D016384:Consensus Sequence; D003509:Cyclohexanecarboxylic Acids / Q000378:metabolism*; D053138:Cyclohexenes; D004247:DNA / Q000378:metabolism*; D000080890:Duocarmycins; D007211:Indoles / Q000378:metabolism*; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D013379:Substrate Specificity
D000970:Antineoplastic Agents; D001572:Benzofurans; D003509:Cyclohexanecarboxylic Acids; D053138:Cyclohexenes; D000080890:Duocarmycins; D007211:Indoles; C076570:carzelesin; C060090:adozelesin; D004247:DNA; D000225:Adenine