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Acid for Basic Peptides, Base for Acidic Ones: A Solubility Rule of Thumb

Not every peptide dissolves in plain water. A simple rule from peptide chemistry helps: first work out whether your peptide is basic, acidic or neutral overall.

Count the charges

Lysine (K) and arginine (R) are positive, as is the N-terminus. Aspartic acid (D) and glutamic acid (E) are negative, as is a free C-terminus. Add them up.

The rule

Net charge Type First thing to try
Positive Basic Water, then a drop of dilute acetic acid
Negative Acidic Water, then a drop of dilute ammonium bicarbonate or base
Near zero Neutral A small amount of organic co-solvent such as DMSO

Why it works

A peptide is least soluble at its isoelectric point, where its net charge is zero. Moving the pH away from that point puts a charge on the molecule, and charged molecules repel each other and dissolve.

An example

DSIP 5mg is a nine-residue peptide with two acidic residues and a free C-terminus, which makes it acidic overall. That is why careful pH choice matters when preparing research solutions.

Always try a small test portion first, and record every change. Keep reading for the next step.

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For laboratory research use only. Not for human or veterinary use, and not intended to diagnose, treat, cure or prevent any condition. This article is educational and is not medical advice.

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