The amino and carboxyl groups of a peptide, and its acidic or basic side chains, gain or lose protons depending on the pH of the solution. At each pH the peptide has a different net charge; the pI is the exact point where positive and negative charges cancel out.
A peptide rich in lysine and arginine has a high (basic) pI; one rich in aspartate and glutamate has a low (acidic) pI. The value is estimated from the sequence and the pKa of each ionisable group.
Near the pI, molecules stop repelling each other by charge and tend to associate: solubility drops to its minimum and cloudiness or aggregates appear. Moving away from the pI, for example by dissolving in a slightly acidic medium, is the classic way to help dissolve difficult peptides.
The pI explains why some peptides dissolve easily in bacteriostatic water while others need a slightly acidic medium. It also determines purification by ion-exchange chromatography.
Related terms
Learn it in depth at the Peptide University
- From amino acid to peptide · Module 1
- The lyophilized form and its diluents · Module 8
- Physical degradation: aggregation and adsorption · Module 11
- Lyophilization and excipients · Module 11
Definition for educational and scientific purposes. It is not medical advice or a recommendation for use. NeoPeptidos products are sold labelled for research use only (RUO).