Article ; Online: Drug design and DNA structural research inspired by the Neidle laboratory: DNA minor groove binding and transcription factor inhibition by thiophene diamidines.
Bioorganic & medicinal chemistry
2022 Volume 68, Page(s) 116861
Abstract: The understanding of sequence-specific DNA minor groove interactions has recently made major steps forward and as a result, the goal of development of compounds that target the minor groove is an active research area. In an effort to develop biologically ...
| Abstract | The understanding of sequence-specific DNA minor groove interactions has recently made major steps forward and as a result, the goal of development of compounds that target the minor groove is an active research area. In an effort to develop biologically active minor groove agents, we are preparing and exploring the DNA interactions of diverse diamidine derivatives with a 5'-GAATTC-3' binding site using a powerful array of methods including, biosensor-SPR methods, and X-ray crystallography. The benzimidazole-thiophene module provides an excellent minor groove recognition component. A central thiophene in a benzimidazole-thiophene-phenyl aromatic system provides essentially optimum curvature for matching the shape of the minor groove. Comparison of that structure to one with the benzimidazole replaced with an indole shows that the two structures are very similar, but have some interesting and important differences in electrostatic potential maps, the DNA minor groove binding structure based on x-ray crystallographic analysis, and inhibition of the major groove binding PU.1 transcription factor complex. The binding K |
|||||
|---|---|---|---|---|---|---|
| MeSH term(s) | Benzimidazoles/chemistry ; Binding Sites ; DNA/chemistry ; Drug Design ; Indoles/pharmacology ; Models, Molecular ; Nucleic Acid Conformation ; Pentamidine/chemistry ; Surface Plasmon Resonance ; Thiophenes/chemistry ; Thiophenes/pharmacology ; Transcription Factors | |||||
| Chemical Substances | Benzimidazoles ; Indoles ; Thiophenes ; Transcription Factors ; Pentamidine (673LC5J4LQ) ; DNA (9007-49-2) | |||||
| Language | English | |||||
| Publishing date | 2022-05-31 | |||||
| Publishing country | England | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural | |||||
| ZDB-ID | 1161284-8 | |||||
| ISSN | 1464-3391 ; 0968-0896 | |||||
| ISSN (online) | 1464-3391 | |||||
| ISSN | 0968-0896 | |||||
| DOI | 10.1016/j.bmc.2022.116861 | |||||
| Shelf mark |
|
|||||
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 3815: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.