To make a protein, we simply covalently link individual amino acids together via a peptide bond. The figure below shows the formation of a peptide bond.

I’d like to draw your attention to two things. First, note that the carboxyl group of one amino acid reacts with the amino group of the second amino acid to form the peptide bond (highlighted in the orange box). This creates a dipeptide with differing ends. At the N-terminal end, there is a free amino group and the C-terminal end has a free carboxyl group. This simply means we can attached a third amino acid to the C-terminal end of the dipeptide with the very same reaction. And if we can add a third, we can add a fourth. Etc. Thus, the structure of the amino acid is perfectly poised to create a growing chain whose length would be determined by factors other than amino acid structure. We can thus begin to catch a glimpse of one reason why proteins are so versatile, as the relative ease of construction is coupled to an ability to vary the length.

But let us now consider something that is even more interesting. Notice the two R groups, R1 and R2. These represent the side chains of each respective amino acid that we briefly discussed in the previous essay. What you should notice is that side chains do not participate in the linking of amino acids. On the contrary, they simply stick out as appendages on the backbone chain of amino and carboxyl groups. And because they do not participate in this linkage, it means that the sequence of side chains is not chemically determined by the process of polymerization. In essence, it is programmable.

These exact same themes are represented in nucleic acids, RNA and DNA. In these cases, the building blocks are more complex and known as nucleotides.

Above is a figure of a nucleotide, showing its three parts: the pentose sugar, a phosphate group, and the nitrogenous base. The nitrogenous base is the analog of the amino acid’s side chain, only this time there are four types: uracil (U), guanine (G), cytosine (C), and adenine (A) in RNA and thymine (T), guanine (G), cytosine (C), and adenine (A) in DNA.

The nucleotides are linked together into a chain through interactions between the phosphate group of one nucleotide and the sugar of an adjacent nucleotide. We’ll call this covalent bond the sugar-phosphate bond and the resulting chain is shown in the following figure:

Notice that as with proteins, the ends are different. The top end contains a free phosphate group and is called the 5’ end (because that phosphate group is bonded to the 5’ carbon of the sugar). The bottom end with the exposed sugar is called the 3’ end. To grow the strand, we need to attach a fourth nucleotide to the 3’ end. Thus, the structure of the more complex nucleotide is perfectly poised to create a growing chain whose length would be determined by factors other than nucleotide structure.

But notice also the way the nitrogenous bases mimic the R groups of amino acids: they do not participate in the formation of the sugar-phosphate bond. On the contrary, they simply stick out as appendages on the sugar-phosphate backbone. And because they do not participate in this linkage, it means that the sequence of nitrogenous bases is not chemically determined by the process of polymerization. In essence, it is programmable.

Thus, what we have is a profound conceptual similarity between two unrelated molecules. It is this similarity in basic format that will allow the nucleic acids to encode the amino acid sequence of a protein.

In the next essay, we’ll see how the similarities begin to diverge only to reunite in a most remarkable manner.