Sequence-selectivity of 5,11-dimethyl-5 H -indolo[2,3- b ]quinoline binding to DNA. Footprinting and molecular modeling studies
| Autor: | Osiadacz J, Jerzy Majka, Kamil Czarnecki, Wanda Peczyńska-Czoch, W. Andrzej Sokalski, Jolanta Zakrzewska-Czerwińska, Łukasz Kaczmarek |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Base Sequence Molecular model Stereochemistry Molecular Sequence Data Organic Chemistry Clinical Biochemistry Intercalation (chemistry) Quinoline DNA Footprinting Nucleic acid sequence Pharmaceutical Science DNA footprinting DNA DNA topoisomerase II activity Biochemistry Footprinting chemistry.chemical_compound chemistry Drug Discovery Molecular Medicine Molecular Biology Carbolines |
| Zdroj: | Bioorganic & Medicinal Chemistry. 8:937-943 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/s0968-0896(00)00031-6 |
| Popis: | Indolo[2,3- b ]quinolines are a new family of the DNA intercalators showing significant cytotoxic activity. The mechanism of their action is based on the inhibition of DNA topoisomerase II activity. It depends on their ability to induce and stabilize drug–topII–DNA cleavable complexes. Site-specific intercalation of 5,11-dimethyl-5 H -indolo[2,3- b ]quinoline (DiMIQ) was analyzed in vitro by DNaseI footprinting and by molecular modeling. To model the DNA–intercalator complex, use was made of the CVFF and ESFF force fields implemented in Insight 97.0 software. Experimental results were verified using a simple statistical model. The DiMIQ molecule was found to bind preferentially to the pBR322 DNA plasmid in the 5′-TGCTAACGC-3′ region between adjacent adenine bases. |
| Databáze: | OpenAIRE |
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