Glossary
TFA Salt
Most synthetic peptides are supplied as trifluoroacetate salts. How much of the vial mass is counter-ion, and when TFA can interfere with cell-based assays.
A TFA salt is a peptide delivered with trifluoroacetate as the counter-ion balancing the positively charged basic residues of the sequence. It is the standard form because trifluoroacetic acid serves both to release the peptide from the resin at the end of SPPS and as the ion-pairing reagent in preparative reversed-phase HPLC — so unless it is exchanged on purpose, it accompanies the peptide through every later step.
What the TFA form means for your work
There are two consequences. The first concerns mass balance: depending on the number of basic residues, TFA usually makes up roughly 10% to 25% of the gross weight, so a vial labelled 5 mg can contain noticeably less than 5 mg of actual peptide. Every molarity calculation should thus begin with the net peptide content from the certificate of analysis rather than with the label value.
The second concerns assay interference. Residual TFA has been reported to be toxic to certain cell lines and to disturb proliferation readouts at levels far below those that damage the peptide, so cell-based studies frequently require the acetate salt instead. TFA additionally gives a distinctive infrared band that can complicate spectroscopic measurements. See reading a COA.
Related terms
purity · excipient · synthetic