期刊
NUCLEIC ACIDS RESEARCH
卷 35, 期 1, 页码 307-316出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkl1025
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资金
- NATIONAL CANCER INSTITUTE [R01CA107311] Funding Source: NIH RePORTER
- NCI NIH HHS [CA107311, R01 CA107311] Funding Source: Medline
Hairpin polyamide-chlorambucil conjugates containing an alpha-diaminobutyric acid (alpha-DABA) turn moiety are compared to their constitutional isomers containing the well-characterized gamma-DABA turn. Although the DNA-binding properties of unconjugated polyamides are similar, the alpha-DABA conjugates display increased alkylation specificity and decreased rate of reaction. Treatment of a human colon carcinoma cell line with alpha-DABA versus gamma-DABA hairpin conjugates shows only slight differences in toxicities while producing similar effects on cell morphology and G(2)/M stage cell cycle arrest. However, striking differences in animal toxicity between the two classes are observed. Although mice treated with an alpha-DABA hairpin polyamide do not differ significantly from control mice, the analogous gamma-DABA hairpin is lethal. This dramatic difference from a subtle structural change would not have been predicted.
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