Amino Acid Side Chains and Reactivity

Amino acid side chains, or R-groups, are the defining feature of each amino acid, providing chemical diversity that allows peptides and proteins to carry out a wide range of biological functions. The reactivity of these side chains is a key determinant of peptide behavior in synthesis and function.

Classification of Side Chains

Amino acid side chains can be classified into several categories based on their chemical properties: non-polar, polar, acidic, and basic. Non-polar side chains, such as those in alanine, valine, and leucine, are hydrophobic and tend to cluster together in the interior of proteins. Polar side chains, like those in serine and threonine, can form hydrogen bonds and are often found on the surfaces of proteins. Acidic side chains, such as those in aspartic acid and glutamic acid, donate protons and play roles in catalysis and metal ion coordination, while basic side chains, such as those in lysine and arginine, accept protons and are often involved in binding negatively charged molecules like DNA.¹

Reactivity in Peptide Synthesis

The reactivity of side chains is also a key factor in peptide synthesis. Some side chains, particularly those with reactive hydroxyl, amine, or carboxyl groups, need to be protected during synthesis to prevent unwanted side reactions. Protecting groups such as the tert-butyloxycarbonyl, Boc group for amines or benzyl (Bn) groups for hydroxyls are often used to temporarily block reactive side chains, ensuring that peptide bonds form only between the desired sites.

Conclusion

The reactivity of amino acid side chains is central to both peptide synthesis and protein function. By understanding the chemical properties of side chains, researchers can design peptides with specific activities and control reactions during synthesis, paving the way for the development of novel peptides with tailored functions.

Citations and Links

1. Berg, Jeremy M., et al. Biochemistry. 8th ed., W.H. Freeman, 2015.