Friday, May 23, 2014

Molecule with Anti-Cancer Kick

In 2013, medical researchers found a molecule that fights cancer in animals by boosting the cell's production of a powerful natural antitumor protein known as TRAIL. The Researchers referred to this anti-cancer molecule as TIC10, short for TRAIL Inducing Compound number 10.
The structure of this molecule, as confirmed by mass spectroscopy, was published at this time as is shown below:
Chemists at The Scripps Research Institute (TSRI) found a way to synthesize this molecule in the laboratory. However, when the Chemists gave their molecule to Biologists to test on cancer cells, this molecule failed to show any anti-cancer activity!
So, the Chemists asked the Biologists to supply some of the TIC10 that had shown anti-cancer activity. The Chemists spent months analyzing both TIC10 molecules to determine their exact molecular structure. And they discovered that the molecule the biologists had shown to fight cancer did not have the structure that was originally published, so the molecule that the Chemists had synthesized in their laboratory would not fight cancer cells,.
However, the Chemists found that the molecule that DOES fight cancer cells has a very similar structure. The structure of the active molecule is shown below:

Note that the structure originally published for TIC10 had the three nitrogen containing rings in a straight line. This new, correct, structure for TIC10 has two of the nitrogen containing rings in a straight line, but the third ring sticks out at an angle from the other two. Only this "angular" isomer (the molecule with a kick) shows any anti-cancer activity.

Kim D. Janda, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI has been quoted as saying, "One lesson from this has got to be: don't leave your chemists behind".

Nicholas T. Jacob, Jonathan W. Lockner, Vladimir V. Kravchenko, Kim D. Janda. Pharmacophore Reassignment for Induction of the Immunosurveillance Cytokine TRAIL. Angewandte Chemie, 2014; DOI: 10.1002/ange.201402133

Further Reading
Molecular Formula  
Condensed Structural Formula 
2-Dimensional Structural Formula
Skeletal Formula
Percent Composition
Functional Groups
Mass Spectroscopy for Structural Determination

Suggested Study Questions:
  1. Refer to the structure of TIC10 as shown above. In one molecule, how many
    • carbon atoms are present?
    • hydrogen atoms are present?
    • oxygen atoms are present?
    • nitrogen atoms are present?
  2.  Write the molecular formula for a molecule of TIC10.
  3. For the TIC10 molecule, calculate the percent by mass of
    • carbon
    • hydrogen
    • oxygen
    • nitrogen
  4. Convert the skeletal structure for the active anti-cancer molecule into a 2-dimensional structural formula.
  5. Circle one benzene ring in the structure of the active anti-cancer molecule.
  6. Circle and name the functional group containing an oxygen atom on the active anti-cancer molecule.
  7. What value do you expect for the mass-to-charge (M/Z) peak on a mass spectrum of the anti-cancer TIC10 compound ?
  8. Do you think mass spectroscopy alone could be used to distinguish between the two structures proposed for TIC10 above? Explain your answer.

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