4.12 : כיראליות בטבע

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.