| Autor: |
Rege, K., Ladiwala, A., Hu, S., Breneman, C. M., Dordick, J. S., Cramer, S. M. |
| Zdroj: |
Journal of Chemical Information and Modeling; November 2005, Vol. 45 Issue: 6 p1854-1863, 10p |
| Abstrakt: |
We have recently developed a novel multivalent cationic library based on the derivatization of aminoglycosides by linear polyamines. In the current study, we describe the DNA-binding activity of this library. Screening results indicated that several candidates from the library showed high DNA-binding activities with some approaching those of cationic polymers. Quantitative Structure−Activity Relationship (QSAR) models of the screening data were employed to investigate the physicochemical effects governing polyamine−DNA binding. The utility of these models for the a priori prediction of polyamine−DNA-binding affinity was also demonstrated. Molecular descriptors selected in the QSAR modeling indicated that molecular size, basicity, methylene group spacing between amine centers, and hydrogen-bond donor groups of the polyamine ligands were important contributors to their DNA-binding efficacy. The research described in this paper has led to the development of new multivalent ligands with high DNA-binding activity and improved our understanding of structure−activity relationships involved in polyamine−DNA binding. These results have implications for the discovery of novel polyamine ligands for nonviral gene delivery, plasmid DNA purification, and anticancer therapeutics. |
| Databáze: |
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