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Definition

A weak acid solution, often 0.1–1%, used to help dissolve basic or aggregation-prone peptides.

Dilute acetic acid, typically 0.1% to 1% in water, is a common reconstitution aid for peptides that dissolve poorly in neutral water. Peptides carrying a net positive charge, from lysine, arginine or histidine, become more fully protonated at low pH, which increases repulsion between molecules and improves solubility. Acidic conditions can also break up aggregates formed during lyophilisation. The usual approach is to dissolve the peptide in a small volume of dilute acid, then dilute further with water or buffer to the working concentration. Acetic acid is volatile and compatible with HPLC and mass spectrometry. Acidic peptides, by contrast, often dissolve better in dilute ammonium bicarbonate or another mild base.

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