19/08/2022
𝐒𝐜𝐢𝐞𝐧𝐭𝐢𝐬𝐭 𝐞𝐱𝐩𝐥𝐚𝐢𝐧𝐬 𝐡𝐨𝐰 𝐝𝐫𝐮𝐠𝐬 𝐰𝐢𝐭𝐡 𝐭𝐡𝐞 𝐬𝐚𝐦𝐞 𝐜𝐡𝐞𝐦𝐢𝐜𝐚𝐥 𝐩𝐫𝐨𝐩𝐞𝐫𝐭𝐢𝐞𝐬 𝐜𝐚𝐧 𝐡𝐚𝐯𝐞 𝐝𝐫𝐚𝐬𝐭𝐢𝐜𝐚𝐥𝐥𝐲 𝐝𝐢𝐟𝐟𝐞𝐫𝐞𝐧𝐭 𝐞𝐟𝐟𝐞𝐜𝐭𝐬
Drugs' conversion between different isomers could actually lead to unexpected effects.
The effects a drug or chemical compound has on the body depend on how its atoms are arranged in space. Some compounds have a dark twin with the same molecular formula but a different 3D structure – and this can have consequences for what they do or don’t do in the body.
Consider the tragic story of thalidomide, a morning sickness drug that caused thousands of birth defects and miscarriages. While one form, or isomer, of thalidomide has a sedative effect, the other is thought to cause abnormal physiological development. Because the two versions can convert back and forth in the body, it’s dangerous to take either form of thalidomide while pregnant.
My research has focused on one such compound found in red grapes and peanuts, resveratrol. It has been a scientific mystery why clinical trials on using resveratrol to treat Alzheimer’s disease have had inconsistent results. Turns out, it may be because two different forms were used – while one may help with cognition and memory, the other may be toxic to the nervous system.
𝐈𝐬𝐨𝐦𝐞𝐫𝐬 𝐚𝐧𝐝 𝐚𝐦𝐢𝐧𝐨 𝐚𝐜𝐢𝐝𝐬
Many drugs have the same atoms and bonds but are arranged differently in space. These drugs are called chiral compounds – meaning they exist as two non-superimposable mirror images. For example, your hands are also non-superimposable mirror images of each other. Although they look the same, they don’t overlap when you put one on top of the other.
Usually, these mirror-image versions have very similar properties because they share the same elements and bonds. But the way they are arranged in space can drastically change the effects they have in the body. Just as you wouldn’t be able to fit a left-handed glove on your right hand, a left-handed version of a drug wouldn’t be able to fit into a target in the body shaped to fit a right-handed molecule.
Chiral molecules come in two versions, or isomers, defined by their optical activity. This means that if you shine polarized light on a chiral molecule, one will rotate the light to the left (indicated by the prefix L-, or levorotatory) while the other will rotate it to the right (indicated by the prefix D, or dextrorotatory).
Amino acids, the building blocks of proteins, are chiral molecules. Living organisms primarily make proteins from amino acids with L configurations. The D configuration, however, has many other functions in nature. Bacteria, for example, use D configuration amino acids to make their cell walls. Mammals use D configuration amino acids as messengers in their nervous and endocrine systems.
