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Conjugation of a Hairpin Pyrrole-Imidazole Polyamide to a Quinone Methide for Control of DNA Cross-Linking

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dc.contributor.author Kumar, Dalip
dc.date.accessioned 2021-10-27T04:22:46Z
dc.date.available 2021-10-27T04:22:46Z
dc.date.issued 2004
dc.identifier.uri https://pubs.acs.org/doi/10.1021/bc049941h
dc.identifier.uri http://dspace.bits-pilani.ac.in:8080/xmlui/handle/123456789/3082
dc.description.abstract A series of quinone methide precursors designed for DNA cross-linking were prepared and conjugated to a pyrrole-imidazole polyamide for selective association to the minor groove. Although reaction was only observed for DNA containing the predicted recognition sequence, yields of strand alkylation were low. Interstrand cross-linking was more efficient than alkylation but still quite modest and equivalent to that generated by a comparable conjugate containing the N-mustard chlorambucil. Varying the length of the linker connecting the polyamide and quinone methide derivative did not greatly affect the yield of DNA cross-linking. Instead, intramolecular trapping of the quinone methide intermediate by nucleophiles of the attached polyamide appears to be the major determinant that limits its reaction with DNA. Self-adducts of the quinone methide conjugate form readily and irreversibly as detected by a combination of chromatography and mass spectroscopy. This result is unlike comparable self-adducts observed for oligonucleotide conjugates that form more slowly and remain reversible. Equivalent intramolecular alkylation of a polyamide by its attached chlorambucil mustard was not observed under similar condition. The presence of DNA, however, did facilitate hydrolysis of this mustard conjugate. en_US
dc.language.iso en en_US
dc.publisher ACS en_US
dc.subject Chemistry en_US
dc.subject Amides en_US
dc.subject Quinones en_US
dc.subject Genetics en_US
dc.title Conjugation of a Hairpin Pyrrole-Imidazole Polyamide to a Quinone Methide for Control of DNA Cross-Linking en_US
dc.type Article en_US


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