Design of a Hairpin Polyamide, ZT65B, for Targeting the Inverted CCAAT Box (ICB) Site in the Multidrug Resistant (MDR1) Gene
| Autor: | W. David Wilson, Caroline O'Hare, Daniel Hochhauser, Zarmeen T. Taherbhai, Moses Lee, Suzanna L. Bailey, Cameron M. Howard, Binh Nguyen, Karen L. Buchmueller, John A. Hartley |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Base pair
Oligonucleotides CAAT box Antineoplastic Agents Biochemistry DNA-binding protein chemistry.chemical_compound Antigens Neoplasm Humans Picolinic Acids Promoter Regions Genetic Molecular Biology Gene Base Sequence biology Oligonucleotide Topoisomerase Organic Chemistry Ligand (biochemistry) Molecular biology Drug Resistance Multiple DNA-Binding Proteins Nylons DNA Topoisomerases Type II chemistry Drug Design Picolines biology.protein Nucleic Acid Conformation Molecular Medicine Genes MDR DNA |
| Zdroj: | ChemBioChem. 6:2305-2311 |
| ISSN: | 1439-4227 |
| Popis: | A novel hairpin polyamide, ZT65B, containing a 3-methylpicolinate moiety was designed to target the inverted CCAAT box (ICB) of the human multidrug resistance 1 gene (MDR1) promoter. Binding of nuclear factor-Y (NF-Y) to the ICB site upregulates MDR1 gene expression and is, therefore, a good target for anticancer therapeutic agents. However, it is important to distinguish amongst different promoter ICB sites so that only specific genes will be affected. All ICB sites have the same sequence but they differ in the sequence of the flanking base pairs, which can be exploited in the design of sequence-specific polyamides. To test this hypothesis, ten ICB-containing DNA hairpins were designed with different flanking base pairs; the sequences ICBa and ICBb were similar to the 3'-ICB site of MDR1 (TGGCT). Thermal-denaturation studies showed that ZT65B effectively targeted ICBa and ICBb (DeltaTM=6.5 and 7.0 degrees C) in preference to the other DNA hairpins ( |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text