Phosphodiester bond

Place in the structure of nucleic acids

Nucleic acids are built from repeating structural units—nucleotides. Their order of succession determines the primary structure of the molecule. To understand how the 3',5'-phosphodiester bond arises, we must examine the assembly sequence of these monomers:

1. First, a nitrogenous base (purine or pyrimidine) binds to a pentose sugar. This forms a nucleoside.
2. Phosphate groups attach to the nucleoside, turning it into a nucleotide.
3. Finally, nucleotides enter into a polycondensation reaction with the release of a water molecule (H₂O). It is at this stage that a phosphodiester bond arises between adjacent monomers, forming the polynucleotide chain.

Bond mechanism and prime notation rule

The bond is called a 3',5'-phosphodiester bond because it throws a chemical "bridge" between strictly defined atoms of adjacent nucleotides. It connects the 3'-carbon of the pentose of the previous unit to the 5'-phosphate of the subsequent one.

Important: Primes (3', 5') in nomenclature are used exclusively to number carbon atoms in the pentose molecule (ribose or deoxyribose). This rule was introduced to clearly distinguish the carbon skeleton of the sugar from the atoms that make up the nitrogenous bases.

Chain polarity and writing rules

Due to the specific arrangement of phosphodiester bonds, the polynucleotide chain acquires strict polarity. It always has two distinct ends:

• 5'-end: contains a free phosphate residue.
• 3'-end: contains a free hydroxyl group (–OH) of the pentose.

In biochemistry, strict rules of notation for the primary structure are adopted:

• The sequence is always written from left to right.
• Reading starts with the nucleotide that has a free 5'-phosphate end (located on the left).
• The record ends with the nucleotide having a free –OH group at the 3'-end (on the right).
• A single-letter code is used to designate nucleotides.

Differences from other chemical bonds

In the structure of nucleic acids, the phosphodiester bond works in combination with other types of interactions. To avoid confusing them, let us review all bonds in the molecule:

• N-glycosidic bond: holds the nitrogenous base at the 1'-carbon of the pentose within a single nucleotide.
• 5'-phosphoester bond: attaches the phosphate group to the 5'-carbon of the pentose (also within a single monomer).
• 3',5'-phosphodiester bond: stitches monomers together into a single chain.
• Hydrogen bond: connects two completed polynucleotide chains to each other according to the principle of complementarity (Adenine—Thymine, Guanine—Cytosine), forming the DNA double helix. Here, the chains are arranged antiparallel: the 5'-end of one chain lies strictly opposite the 3'-end of the other.

Effect of pentose on structure (DNA and RNA)

Although the mechanism of phosphodiester bond formation is universal, DNA and RNA chains themselves differ in sugar structure. The difference lies in the substituent (X) at the 2'-carbon atom of the pentose:

• If X = H, we have deoxyribose, characteristic of DNA. This molecule is responsible for storing hereditary information and transmitting it via replication. It is localized predominantly in the cell nucleus (in eukaryotes) or in the nucleoid (in prokaryotes).
• If X = OH, it is ribose, which is part of RNA, participating in the realization of genetic information (protein synthesis).

Class and exam questions

What else to study on this topic

• Principle of nitrogenous base complementarity (A-T, G-C)
• Hydrogen bonds and formation of the DNA double helix
• Differences between ribose and deoxyribose (substituent at the 2'-carbon)
• Taxonomic significance of GC pairs in bacteria
• N-glycosidic bond and nucleoside formation

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.