a sequence specific threading tetra intercalator with an extremely slow dissociation rate constant
Download
Skip this Video
Download Presentation
Photo/quote source: web5s.utexas/news/2012/02/dna-wranglers/

Loading in 2 Seconds...

play fullscreen
1 / 21

Photo/quote source: web5s.utexas/news/2012/02/dna-wranglers/ - PowerPoint PPT Presentation


  • 58 Views
  • Uploaded on

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.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Photo/quote source: web5s.utexas/news/2012/02/dna-wranglers/' - doctor


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
a sequence specific threading tetra intercalator with an extremely slow dissociation rate constant

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

slide2
“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/

what is a threading intercalator
What is a threading Intercalator?
  • A molecule that is capable of binding and inserting itself into a DNA sequence.
  • Sequence specific binding
    • 5’ – GATAAGTACTTATC – 3’

http://sketchfu.com/drawing/1919089-snake-and-ladder-

why is this important
Why is this important?

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

tetra intercalator 3
Tetra-intercalator 3
  • Designed with a minor-major-minor groove binding linkers
  • Tetra-intercalator 3 was designed using studies done previously on 1 and 2.
  • -βAla3-Lys- is the minor groove binding linker taken from bisintercalator 2.
  • Adipic acid with 2 L-Lysine residues are part of the major groove binding linker.
    • Causes C2 symmetry that simplifies the NMF
  • 14 Basepair binding site.
  • Pieced together by connecting together NDI units
how to make a tetra intercalator
How to make a tetra-intercalator

http://io9.com/5885072/dna+tangling-molecule-could-revolutionize-treatments-for-cancer-and-hiv

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

napthalenetetracarboxylic diimide
Napthalenetetracarboxylic diimide
  • NDI units can be pieced together in different ways
  • The different arrangements then must be scanned in order to find the sequences the new arrangements will select for

http://www.chemspider.com/Chemical-Structure.24771033.html

slowed dissociation rate
Slowed Dissociation Rate

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

threading bisintercalators 1 2
Threading bisintercalators 1&2
  • figure 1a picture here
  • figure 1b picture here.
threading polyintercalator of 3
Threading Polyintercalator of 3

Show extremely slow dissociation from its preferred DNA sequence.

Association is suspected to be rapid result of electrostatic interactions.

association rate measurements
Association rate measurements

1H NMR spectroscopy,

Gel mobility shift assay and

stopped-flow ultraviolet–visible spectroscopy.

conclusion
Conclusion

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.

work cited
Work Cited

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

work cited cont
Work Cited Cont.

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

ad