phosphodiester
Summary
A phosphodiester is a phosphate group esterified to two alcohol groups, R–O–P(O)(O⁻)–O–R′. In DNA and RNA, phosphodiester bonds join the 3′ OH of one nucleotide to the 5′ phosphate of the next. They form the covalent, negatively charged backbone.
Detail
Meaning: Phosphoric acid has three OH groups. When two are esterified with alcohols, the product is a phosphodiester. The remaining OH is acidic and is deprotonated at physiological pH, so each linkage carries a negative charge. In nucleic acids, the 3′ hydroxyl of one sugar attacks the phosphate of an incoming nucleoside triphosphate, forming the bond and releasing pyrophosphate. Hydrolysis of that pyrophosphate helps drive the reaction forward. This gives every strand a 5′ end (free phosphate) and a 3′ end (free OH). Phospholipids also contain a phosphodiester, linking glycerol to an alcohol head group such as choline.
On the MCAT: You may be asked to pick out the backbone in a drawn structure, name the free ends of a strand, or explain why DNA is polyanionic. That charge explains why DNA binds positively charged histone proteins and migrates toward the positive electrode in gel electrophoresis. Passages may also compare RNA and DNA: the 2′ OH of RNA can attack the neighboring phosphorus, so RNA is hydrolyzed more easily than DNA, especially in base.
Common confusion: Students mix up phosphodiester bonds with hydrogen bonds and with phosphoanhydride bonds. Hydrogen bonds pair the bases between strands, and heating breaks them while leaving the backbone intact. Phosphoanhydride bonds join the phosphates in ATP. "Di" means two ester bonds on one phosphate, not two phosphates.
Sources
- Organic Chemistry (Clayden)
- Lehninger Principles of Biochemistry
- Organic Chemistry (Wade)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.