A sequence-specific threading tetra-intercalator with an extremely slow dissociation rate constant. Article by: Garn F. Holman, Maha Zewail-Foote, Amy Rhoden Smith, Kenneth A. Johnson, and Brent L. Iverson Presentation by: Maggie Palmer and Joy Uyanwune.
Article by: Garn F. Holman, Maha Zewail-Foote, Amy Rhoden Smith, Kenneth A. Johnson, and Brent L. Iverson
Presentation by: Maggie Palmer and Joy Uyanwune
“If you think of DNA as a spiral staircase imagine sliding something between the steps. That’s what our molecule does. It can be visualized as binding to DNA in the same way a snake might climb a ladder.” ~Brent L. Iverson
Photo/quote source: http://web5.cns.utexas.edu/news/2012/02/dna-wranglers/
Molecules that can bind to DNA can interfere and possibly control transcription, repair and replication.
Possible cure for chronic diseases
Photo source: http://www.nature.com/nchem/journal/v3/n11/full/nchem.1173.html
Naphthalenetetracarboxylic diimide (NDI) molecules are chained together with resin beads.
Reactions are ran directly on the resin beads until the molecule is large enough to cleave.
“The larger molecule is composed of little pieces that bind to short segments of DNA, kind of life the way Legos fit together” ~Amy Rhoden-Smith
Picture source: Lee et.al something between the steps. That’s what our molecule does. It can be visualized as binding to DNA in the same way a snake might climb a ladder.” ~Brent L. Iverson
3 will have a slow dissociation from its preferred DNA binding site.
In order for 3 to fully dissociate from DNA it the individual units will have to dissociate in an ordered fashion before rebinding occurs.
Photo source: http://mysam.net/wiki/index.php/%ED%8A%B9%EC%88%98%EA%B8%B0%EB%8A%A5:NatureNews?reply=4&page=1
Show extremely slow dissociation from its preferred DNA sequence.
Association is suspected to be rapid result of electrostatic interactions.
Stopped Flow Method
1H NMR spectroscopy,
Gel mobility shift assay and
stopped-flow ultraviolet–visible spectroscopy.
Tetra-intercalator 3 has a slow dissociation rate.
The half life of tetra-intercalator 3 was found to be16 days.
Tetra-intercalator 3 also shows a rapid association rate to its target specific sequence driven by electrostatic attraction.
Suspected to have the same threading topology on long pieces of DNA.
Holman, Garen G., Zewail-Foote, Maha; Smith, Amy Rhoden; Johnson, Kenneth A.; & Iverson, Brent L. 2001. A Sequence-specific threading teta-intercalator with an extremely slow dissociation rate constant. Nature Chemistry. 3; 875-881
Lee, J.; Guelev, V.; Sorey, S.;Hoffman, D.W. &Iverson, B.L.2004 NMR Structural analysis of a modular threading tetraintercalator bound to DNA. J. Am. Chem. Soc, 126; 14036-14042
Oppenheimer, Daniel. 2012 DNA- Targeting Molecule has Potential to Help Treat Genetic Disease and HIV. Online at. http://web5.cns.utexas.edu/news/2012/02/dna-wranglers