Stereochemistry in biomolecules

Introduction to Stereochemistry in Biomolecules

Stereochemistry refers to the study of different spatial arrangement of atoms in molecules.
The arrangement of atoms in space is crucial in biomolecules as it affects their properties and functioning.

Chiral molecules are those that cannot be superimposed onto their mirror image.
Stereoisomers are isomers that differ in the spatial arrangement of atoms. There are two main types: enantiomers and diastereomers.
Enantiomers are mirror images of each other, like left and right hand. They are single chiral centres and are non-superimposable.
Diastereomers are not mirror images. They contain two or more chiral centres and can have different physical properties.

Chirality is necessary for many biological processes. Biomolecules interacting with each other often recognize ‘the right hand from the left hand’.
Biological systems usually contain and react with only one enantiomer, known as chiral specificity. This is seen in the way living systems utilise L-amino acids and D-sugars.

Stereoisomers are named using Cahn-Ingold-Prelog (CIP) system wherein priorities are given to different groups attached to the chiral carbon.
The groups are ordered 1, 2, 3, and 4 based on atomic number of the atom directly attached to chiral carbon; the higher the atomic number, the higher the priority.
When the lowest priority (4) is at the back, if the order from 1-2-3 is counter-clockwise, it represents S (sinister), and if clockwise, it represents R (rectus).

The configuration of molecules in drug design is critical as different enantiomers of a drug can have drastically different effects.
The infamous thalidomide case underlines the importance of chirality in biochemistry. One enantiomer of thalidomide was a useful sedative and anti-nausea drug, while the other caused severe birth defects.
Hence, understanding stereochemistry is crucial for safe and effective drug design.

The D/L system is used to designate the configuration of sugars.
It’s based on the configuration of the highest numbered chiral centre - if the OH group is on the right in the Fischer projection, it’s a D-sugar and if on the left, it’s an L-sugar.
An important note is that D-sugars are predominantly found in nature.