Counter-ion
A counter-ion is the oppositely charged ion, most often trifluoroacetate, that pairs with a synthetic peptide's charged residues and stays in the powder as part of its weight.
Synthetic peptides are salts. Their basic residues, such as lysine, arginine and histidine, and the free amino end carry a positive charge, and each charge is balanced by a negative counter-ion. In peptides made by solid-phase synthesis this is most often trifluoroacetate, left over from the trifluoroacetic acid used to cleave the peptide from its resin and in purification. Some suppliers exchange it for acetate or chloride.
Counter-ions are not peptide, so a peptide purity figure does not count them, and HPLC does not see them as peptide peaks. They still add to the weighed mass, which is why net peptide content sits below 100% even in a very pure sample. Sequences with many basic residues carry more counter-ion by weight.
The counter-ion can matter to an experiment as well as to the arithmetic. Research on exchanging trifluoroacetate for chloride has found that counter-ion content varies with sequence and argued that it should be measured and stated for any assay using synthetic peptides.
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UPDATED OCTOBER 26, 2026 · REVIEWED BY DEL POTTER, PHD