Peptide solubility

What drives it

Charged and polar side chains interact favourably with water and help a peptide dissolve. Hydrophobic side chains do not, and a sequence rich in them will resist aqueous solvent and may prefer to associate with other peptide molecules instead — which is aggregation.

Net charge and pH

A peptide is most soluble when it carries net charge, because charged molecules repel each other and stay dispersed. At the pH where positive and negative charges balance, net charge is zero, repulsion disappears and solubility is at its minimum.

This is why the same peptide can dissolve readily in one solvent and precipitate in another of different pH.

Practical signals

• Clear solution: dissolved
• Cloudy or hazy: incompletely dissolved or aggregating
• Visible particles: undissolved material or precipitate
• Gel-like behaviour: association between chains

Concentration

Solubility is a limit, not a property that scales indefinitely. A peptide that dissolves at one concentration may not at a higher one, and the excess will remain undissolved or come out of solution later.