AI Article Synopsis
- A new conjugate combining BQQ and neomycin is developed that effectively stabilizes T.A.T and mixed base DNA triplex structures.
- This conjugate outperforms both components separately and their combination, achieving stabilization at low concentrations (4 μM) in high salt conditions.
- Binding studies indicate a strong preference for the conjugate to attach to triplex DNA/RNA rather than duplex or single strands, with modeling suggesting an interaction in the Watson-Hoogsteen groove.
Article Abstract
Synthesis of a BQQ-neomycin conjugate is reported. The conjugate combines two ligands, one known to intercalate triplexes (BQQ) and another known to bind in the triplex groove (neomycin). The conjugate stabilizes T.A.T, as well as mixed base DNA triplex, better than neomycin, BQQ, or a combination of both. The conjugate selectively stabilizes the triplex (in the presence of physiological salt concentrations), with as little as 4 muM of the ligand leading to a DeltaTm of >60 degrees C. Competition dialysis studies show a clear preference for the drug binding to triplex DNA/RNA over the duplex/single strand structures. Modeling studies suggest a structure of neomycin bound to the larger W-H (Watson-Hoogsteen) groove with BQQ intercalated between the triplex bases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/ja034241t | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Surface Dependent Dual Recognition of a G-quadruplex DNA With Neomycin-Intercalator Conjugates.
Front Chem
February 2020
Laboratory for Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, SC, United States.
G-quadruplexes have been characterized as structures of vital importance in the cellular functioning of several life forms. They have subsequently been established to serve as a therapeutic target of several diseases including cancer, HIV, tuberculosis and malaria. In this paper, we report the binding of aminosugar-intercalator conjugates with a well-studied anti-parallel G-quadruplex derived from G-quadruplex DNA.
View Article and Find Full Text PDFProbing the recognition surface of a DNA triplex: binding studies with intercalator-neomycin conjugates.
Biochemistry
July 2010
Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, South Carolina 29634, USA.
Thermodynamic studies on the interactions between intercalator-neomycin conjugates and a DNA polynucleotide triplex [poly(dA).2poly(dT)] were conducted. To draw a complete picture of such interactions, naphthalene diimide-neomycin (3) and anthraquinone-neomycin (4) conjugates were synthesized and used together with two other analogues, previously synthesized pyrene-neomycin (1) and BQQ-neomycin (2) conjugates, in our investigations.
View Article and Find Full Text PDFCombining the best in triplex recognition: synthesis and nucleic acid binding of a BQQ-neomycin conjugate.
J Am Chem Soc
July 2003
Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, SC 29634, USA.
Article Synopsis
- A new conjugate combining BQQ and neomycin is developed that effectively stabilizes T.A.T and mixed base DNA triplex structures.
- This conjugate outperforms both components separately and their combination, achieving stabilization at low concentrations (4 μM) in high salt conditions.
- Binding studies indicate a strong preference for the conjugate to attach to triplex DNA/RNA rather than duplex or single strands, with modeling suggesting an interaction in the Watson-Hoogsteen groove.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!