4.12: Chirality in Nature

Chirality is the most intriguing yet essential facet of nature, governing life’s biochemical processes and precision. It can be observed from a snail shell pattern in a macroscopic world to an amino acid, the minutest building block of life. Most of the snails around the world have right-coiled shells because of the intrinsic chirality in their genes. All the amino acids present in the human body exist in an enantiomerically pure state, except for glycine - the sole achiral amino acid. The chirality of amino acids has a significant consequence on the symmetry and function of naturally occurring proteins and enzymes. With 268 chiral centers, human chymotrypsin could exist in 2²⁶⁸ possible configurations if each amino acid took either of the enantiomeric forms. However, the role of chirality has ordained a single chiral chymotrypsin as the selective digestive enzyme.

Another critical aspect in the cascade of biochemical processes is that most enzymes interact with only one of the enantiomers due to their chirality. Consequently, enantioselectivity arises, like a lock-and-key mechanism, where only one enantiomer can fit into the enzyme’s binding site. This has a significant implication in the domain of drug design, where each enantiomer can induce a different effect. The role of chirality was brought to light in a devastating way nearly five decades ago when the drug thalidomide was prescribed for the treatment of morning sickness in pregnant women. Ever since, the properties of each enantiomer have been ascertained for every drug designed.

Most interestingly, this facet of chirality extends from the microcosm to the macrocosm. When Pasteur discovered the connection between optical activity and molecular chirality, it led him to conjecture that even the forces of nature are chiral. This has now been proven across the universe in the weak interactions between fundamental particles, which can violate parity symmetry.

Ever noticed the patterns on the shell of a garden snail? In all probability, the shell will be right-coiled. In fact, in London, when a left-coiled snail was discovered, it was so rare that a worldwide campaign was launched to find it a left-coiled mate.

Indeed, almost all snails across the world have right-coiled shells—a consequence of the intrinsic chirality of their genes.

Like snails, most natural products and biomolecules are chiral. For example, all amino acids present in our body exist as single enantiomers, except for the sole achiral amino acid, glycine.

Amino acids are the building blocks of proteins; as such, the chirality of amino acids has significant consequences on the symmetry and function of all naturally occurring proteins and enzymes.

Consider the case of chymotrypsin, a digestive enzyme found in the intestines of many animals. Human chymotrypsin, with 268 amino acids in the sequence, has 268 chiral centers.

If each of these amino acids could exist in either of their two enantiomeric forms, human chymotrypsin would have 2²⁶⁸ possible configurations. Fortunately, amino acids exist as single enantiomers in our body, and accordingly, chymotrypsin is present in only one chiral configuration.

Owing to the chirality of their structure, most enzymes such as chymotrypsin specifically react with only one of the two enantiomers of a molecule. This enantioselectivity arises as only one of the enantiomers can fit in the enzyme’s binding site, analogous to a lock-and-key mechanism.

Accordingly, the enantiomers of a drug molecule can invoke different biological responses in the body. For instance, while the S enantiomer of the drug naproxen has anti-inflammatory properties, the R enantiomer of naproxen is a liver toxin. Thus, naproxen is sold as a single enantiomer.

Some drugs, such as ibuprofen, are sold as racemic mixtures. Here, while the S enantiomer is the active agent, the R enantiomer is inactive and harmless.