du-86 has been researched along with Neoplasms* in 1 studies
1 other study(ies) available for du-86 and Neoplasms
Article | Year |
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C-H to N substitution dramatically alters the sequence-specific DNA alkylation, cytotoxicity, and expression of human cancer cell lines.
We designed and synthesized sequence-specific alkylating conjugates 1 and 2, which selectively alkylate matched sequences at nanomolar concentrations. Conjugates 1 and 2 differ only in that the C-H is substituted by an N in the second ring, which precisely recognizes and effectively alkylates DNA according to the recognition rule of Py-Im polyamides. We investigated sequence-specific DNA alkylation, cytotoxicity in 39 human cancer cell lines, and the effect on expression levels in cancer cell lines by Py-Im conjugates 1 and 2. The COMPARE analysis of the mean graphs showed that conjugates 1 and 2 did not correlate well with each other (r = 0.65) despite having a common DNA alkylating mechanism (purine N3 alkylation). Array-based gene expression analysis demonstrated that there are several oppositely regulated genes. The results suggest the intriguing possibility that DNA alkylating agents recognizing longer base-pair sequences may provide a promising approach for developing new types of antigene agents. Topics: Alkylation; Antineoplastic Agents, Alkylating; Cell Line, Tumor; DNA, Neoplasm; Duocarmycins; Humans; Imidazoles; Neoplasms; Nylons; Pyrroles; Pyrrolidinones; Structure-Activity Relationship; Substrate Specificity | 2004 |