My entire adult life has been spent studying organic chemistry. From graduate school, to the faculty at universities, to working for NASA, I’ve always been amazed by the powerful changes that can be induced by the simplest of molecular change. A large molecule that refuses to dissolve in water can be made completely soluble by a simple negative charge. A compound that turns black and decomposes with exposure to the slightest amount of light can be made completely stable by swapping a hydrogen for a carbon. Flipping the orientation of a molecular bond from one direction to the other is the foundation for human vision. Even the most complicated of molecules can have their behavior radically changed by a seemingly innocuous change of structure, which is something that I absolutely adore about my chosen career path. As a synthetic organic chemist, I have tremendous control over the properties of a compound.
It’s this extraordinary power to modify molecular behavior that may soon prove to be a literal life saver. There is a compound named vancomycin. It’s an antibiotic, and it’s pretty much the “end of the line” when it comes to treatment for infection. It can be risky (as it has side effects) and if it doesn’t work, there really isn’t anything left in the stockpile that doctors can use against bacteria. When vancomycin was first released, there were not many infections that were resistant. However, as time goes on, strains of bacteria gradually develop protection against antibiotics. The problem is that bacteria can multiply so rapidly. Even if an infection treated with vancomycin is 99.999% eradicated, that still leaves a handful of bacteria that were all somehow (random mutation, etc) resistant to the drug. All of those resistant bugs then multiply into billions of resistant bacteria, which can spread to other humans. As a result, vancomycin resistant infections are being a frightening reality, and we don’t have anything left that we can throw at them.
Thankfully, researchers from California have recently disclosed in the Journal of the American Chemical Society that they have succeeded in modifying the vancomycin structure. Normally, vancomysin binds to a portion of the bacteria and prevents the cell from producing the cell wall. Without this crucial cellular component, the bacteria dies and the infection subsides. Resistant bacteria don’t have the necessary chemical handhold for the antibiotic to attack. To combat this, the California chemists modified the vancomycin molecule, replacing a carbon-oxygen double bond with a carbon-nitrogen double bond. It’s the replacement of just one atom from among the hundreds inside the vancomycin molecule, but it completely changes the molecular behavior. The adaptation that resistant bacteria have which protects them from the unaltered drug fails to protect them from the modified medicine, and the new vancomycin derivative can fight off the resistant strain.
We may never completely win the fight against resistant bacteria. They have the advantage of unlimited mutation potential. In order to provide doctors with the medicines they need, organic chemists such as myself have to be clever, and rely on these simple but powerful changes to antibiotic structure in order to defeat the infections. For now at least, humans appear to be winning over the bugs.
The source of this article can be found at:
Xie, J. “A redesigned vancomycin…exhibits potent antimicrobial activity against vancomycin-resistant bacteria”. J. Am. Chem. Soc. 2011, 133, 13946-13949.