What is a polypeptide? Polypeptide chains explained

A polypeptide is a chain of many amino acids joined end to end by peptide bonds. "Poly" means many: a polypeptide has many residues, and so many peptide bonds. Proteins are made of one or more polypeptide chains. This guide looks at the chain itself: its repeating backbone, its side chains, its direction, how it is written down, and how a polypeptide differs from a peptide and a protein.

For the basics of amino acids and how one peptide bond forms, start with what is a peptide. Terms are defined in the glossary.

What is a polypeptide?

A polypeptide is a single, unbranched chain of amino acids. Each amino acid is joined to the next by a peptide bond, the amide link between the carboxyl group of one and the amino group of the next (IUPAC-IUB, 3AA-11).

In plain terms, think of a chain of beads:

• each bead is an amino acid, called a residue once it is part of the chain,
• each link between beads is a peptide bond, and
• each bead has a tag hanging off it, its side chain, which makes it different from the others.

What makes the chain a polypeptide rather than just a peptide is length. There is no sharp line, but IUPAC calls chains of more than about 10–20 residues polypeptides.

Is a polypeptide a protein?

Not always. A protein is made of one or more polypeptide chains folded into a stable shape, so every protein contains polypeptides, but a polypeptide on its own may be too short or too loosely folded to be called a protein.

How many amino acids are in a polypeptide?

There is no fixed number: IUPAC calls chains of more than about 10–20 residues polypeptides, with no upper limit (IUPAC-IUB, 3AA-11). Chains in proteins range from a few dozen residues to tens of thousands, and titin, one of the longest known, is listed at 34,350 residues (UniProt Q8WZ42).

Polypeptide meaning: peptide, polypeptide and protein

The boundaries are conventions, and authors draw them in slightly different places. Two points are worth keeping in mind:

• A polypeptide is one chain. A protein can be one polypeptide, or several polypeptide chains held together. Collagen, for example, is three chains wound into a triple helix (Shoulders and Raines, 2009).
• "Protein" also implies a shape. A protein usually folds into a stable three-dimensional structure. A polypeptide may or may not. See peptide and protein structure.

For which everyday compounds count as peptides at all, see is it a peptide?.

The polypeptide chain: backbone and side chains

Every polypeptide chain has two parts.

The backbone

The backbone is the repeating core of the chain. Each residue adds the same three atoms in the same order:

–N–Cα–C–

• N is the nitrogen from the amino group.
• Cα (alpha carbon) is the central carbon of the amino acid, which carries the side chain.
• C is the carbonyl carbon (C=O) from the carboxyl group.

The C of one residue is joined to the N of the next by the peptide bond. So the backbone reads N–Cα–C–N–Cα–C–N–Cα–C and so on, for as many residues as the chain has. Because the backbone is the same all the way along, it is the side chains that make one polypeptide different from another.

The side chains

Each Cα carries one side chain. There are 20 standard side chains, ranging from a single hydrogen atom (glycine) to large ring systems (tryptophan). They decide a chain's charge, how well it dissolves in water and how it folds. See the 20 amino acids and functional groups in peptides.

How peptide bonds join a polypeptide chain

A polypeptide chain of n residues is held together by n − 1 peptide bonds, so a 30-residue polypeptide has 29.

• One fewer bond than residues. Each bond joins two neighbouring residues, and the two ends of the chain are left free.
• Water is lost at each bond. Forming each peptide bond releases one molecule of water. That is why the mass of a chain is the sum of its amino acids minus 18.02 for every bond. For example, lysine (146.19), proline (115.13) and valine (117.15) add up to 378.47, and taking away two waters (36.03) gives 342.44 g/mol for the tripeptide Lys-Pro-Val. Masses are from PubChem. See molar mass and molecular weight.
• The bond is flat. The C=O and N–H of each peptide bond lie in one plane, and the bond can't rotate freely (Pauling, Corey and Branson, 1951). The chain can only twist at the bonds either side of each Cα. This is what gives polypeptides their regular shapes, such as helices and sheets.
• The bond is stable. In neutral water with no catalyst, a peptide bond takes years to break. See hydrolysis.

For how a single peptide bond forms, and how it relates to amide bonds in general, see what is a peptide.

Direction: N-terminus to C-terminus

A polypeptide chain has a direction, like a sentence.

• One end has a free amino group (–NH₂). This is the N-terminus, or amino end.
• The other end has a free carboxyl group (–COOH). This is the C-terminus, or carboxyl end.

By convention, chains are always written and numbered from the N-terminus to the C-terminus (IUPAC-IUB, conformation of polypeptide chains). Residue 1 is at the N-terminal end. This is also the direction in which cells build polypeptides, adding each new residue to the C-terminal end.

The direction matters. Gly-Ala and Ala-Gly contain the same two amino acids, but they are different molecules, because the free amino group sits on a different residue in each. Either end can also be chemically capped. See C-terminal amides and N-terminal acetylation.

How a polypeptide chain is written

A chain can be written in several ways, all reading from the N-terminus on the left (IUPAC-IUB, 3AA-13). The examples use the tripeptide KPV (Lys-Pro-Val):

The one-letter code is the usual way to write anything longer than a few residues. A 40-residue polypeptide is far easier to read as a 40-letter string than as 40 three-letter codes. See amino acid codes and how to read a peptide sequence.

How polypeptides are made

Cells make polypeptides on ribosomes, reading a genetic template and adding one amino acid at a time to the growing C-terminal end. In the laboratory, polypeptides are usually made by chemical synthesis on a solid support, built in the opposite direction, from the C-terminus to the N-terminus. See solid-phase peptide synthesis.

Chemical synthesis becomes harder as chains get longer, because small losses at each step add up. See percentage yield.

Related guides

For how peptides are named and how long they are, see what is a peptide. For how a chain folds, see peptide and protein structure. For drawing a chain on paper, see reading a structure diagram.