Abstract:
:A series of hairpin pyrrole-imidazole polyamide-fluorescein conjugates were synthesized and assayed for cellular localization. Thirteen cell lines, representing 11 human cancers, one human transformed kidney cell line, and one murine leukemia cell line, were treated with 5 microM polyamide-fluorescein conjugates for 10-14 h, then imaged by confocal laser scanning microscopy. A conjugate containing a beta-alanine residue at the C terminus of the polyamide moiety showed no nuclear localization, whereas an analogous compound lacking the beta-alanine residue was strongly localized in the nuclei of all cell lines tested. The localization profiles of several other conjugates suggest that pyrrole-imidazole sequence and content, dye choice and position, linker composition, and molecular weight are determinants of nuclear localization. The attachment of fluorescein to the C terminus of a hairpin polyamide results in an approximately 10-fold reduction in DNA-binding affinity, with no loss of binding specificity with reference to mismatch binding sites.
journal_name
Proc Natl Acad Sci U S Aauthors
Best TP,Edelson BS,Nickols NG,Dervan PBdoi
10.1073/pnas.2035074100keywords:
subject
Has Abstractpub_date
2003-10-14 00:00:00pages
12063-8issue
21eissn
0027-8424issn
1091-6490pii
2035074100journal_volume
100pub_type
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