The work of the two researchers who have been awarded this year’s Nobel Prize for chemistry solved a complex puzzle of why a molecule, such as an amino acid, is found in two mirror-image forms, but living organisms build proteins using only one of them. Chemistry researchers had to find a pathway through which one of the mirror molecules could be produced in useful volumes in such fields as pharmaceuticals. A major advance in this field by Henri Kagan, now 95 and emeritus professor at the University of Paris-Sud, explained in 1986 that manipulating a catalyst could produce an excess of one of the mirror forms of the molecule based on its own chirality, or handedness. In other words, whether it was left- or right-handed in its orientation.
From Catalysts To Autocatalysis
That discovery was taken forward by Kenso Soai, 76, an emeritus professor at the Tokyo University of Science, who produced conditions nearly two decades later where the catalyst was the molecule itself and it was able to replicate through a process termed autocatalysis. This leap had major implications for drug development, because the proteins that the drug molecules are aimed at respond differently to the two mirror images.
The hazards of drug development were highlighted by the Thalidomide crisis, when this medicine given for morning sickness in pregnancy led to birth defects: one version of the drug molecule, based on its handedness, was safe, and the other was not. Since there was poor understanding of the impacts of the mirror molecules, the drug produced a severe limb deformity in many children. This tragedy led to close testing of drug molecules in terms of their orientation and effects.
Chirality And Drug Development
With the humility and rationality characteristic of true scientists, Prof. Soai said, after being named a laureate, that there was more of the mystery to be solved, including the evolutionary trend of how amino acids express themselves and the evolution of life itself. The development of at least one anti-HIV drug, Efavirenz, through effective synthesis is credited to Kagan’s amplification of a mirror form of a molecule. A Parkinson’s drug, levodopa, also contains one effective—or chiral—molecule of the drug.
Interestingly, the phenomenon at the core of the chemistry prize, the chirality of the molecule, is at work even in the perfume industry, where the intensity, receptivity, and quality of the scent are determined by whether it is left- or right-handed.
Explaining The Basis Of Life
Some observers think this year’s Nobel has come late, since it was anticipated even a quarter century ago; the French science minister issued a protest at Kagan being omitted in 2001. The upshot of the work is the elegant explanation proposed on why the very basis of life is homochiral—amino acids are L-configured, while the sugars forming the DNA and the RNA are the opposite, D-configured.
