What is a counterion?

Most peptides bind counterions and are lyophilized in the form of the corresponding salts. Exceptions are those that do not have basic amino acids such as Arg, Lys, His, and those with a blocked N-terminus. Synthetic peptides that are purified by RP-HPLC are usually obtained as TFA, AcO or HCl salts. Basic amino acid residues and the free N-terminal amine of the peptide are protonated and have trifluoroacetate (TFA) or (CF3COO) Acetate (AcO) or HCl counterions depending upon the final lyophilization buffer. The vast majority of peptide APIs are produced as acetate salts. On rare occasions, they may be prepared as HCl or Na+ salts.

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