Unanticipated differences between α- and γ-diaminobutyric acid-linked hairpin polyamide-alkylator conjugates
Open Access
- 14 December 2006
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 35 (1) , 307-316
- https://doi.org/10.1093/nar/gkl1025
Abstract
Hairpin polyamide–chlorambucil conjugates containing an α-diaminobutyric acid (α-DABA) turn moiety are compared to their constitutional isomers containing the well-characterized γ-DABA turn. Although the DNA-binding properties of unconjugated polyamides are similar, the α-DABA conjugates display increased alkylation specificity and decreased rate of reaction. Treatment of a human colon carcinoma cell line with α-DABA versus γ-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 α-DABA hairpin polyamide do not differ significantly from control mice, the analogous γ-DABA hairpin is lethal. This dramatic difference from a subtle structural change would not have been predicted.Keywords
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