Acid-Base Chemistry of Peptides

Introduction to Protein Structure

Acid-Base Properties of Peptides

All peptides have, as a minimum, two ionizable groups, the amino group of the N-terminal residue, and the carboxyl group of the C-terminal residue. In addition to these groups there may also be ionizable groups in the side chains of some of the amino acids composing the peptide.

Many times, it is important to be able to predict the charge carried by a particular peptide or protein (remember proteins are "simply" large peptides!). This is useful in predicting how a protein (or peptide) will move during electrophoresis or how it will interact with an ion-exchange medium used for chromatography.

Since the charged groups present in amino acids are titratable, it is important to remember that the charge on a peptide (or protein) is dependant on pH. If you do not have a firm grasp on acid-base equlibria, now would be a good time to review this topic.

The overall or net charge on a peptide (or protein) is simply the sum of the charges of every ionizable group in the peptide. Thus determining the charge on a peptide involves three steps:

Identify all of the ionizable groups
Determine the charge on each group at the given pH
Sum the charges

Here are some worked examples:

VILM (example #1)

SEVQ (example #2)

CEPTLKQR (example #3)