TFA-free peptide synthesis

TFA-free peptide synthesis offered

16th December 2025

Submitted by:

Andrew Warmington

Luxembourg Bio Technologies, a supplier of reagents and technologies for peptide synthesis, has announced a new deprotection and cleavage method for solid-phase peptide synthesis (SPPS) that eliminates the use of trifluoroacetic acid (TFA). This technology is based on formic acid combined with in situ–generated hydrochloric acid.

TFA is widely used as a reagent in peptide manufacturing, but, as one of the per- and polyfluoroalkyl substance (PFAS) class of chemicals that is persistent, mobile and resistance to degradation, TFA accumulation has become a subject of regulatory concern and waste containing it also requires specialised disposal methods.

Luxembourg stated that the new system provides broad compatibility with commonly used acid-labile protecting groups, including tert-butyl esters and ethers, Boc, Trt, Pbf and Pmc. It is also said to be applicable to major resin types, such as Wang, Rink Amide, 2-chlorotrityl, Sieber and Ramage. 

Operational advantages may include simplified downstream processing, reduced counter-ion exchange steps and lower waste-handling expenses. Technical evaluations have shown that the process can deliver high crude purity and yield while maintaining low levels of racemisation, the company added. The method is suited to both laboratory and industrial applications and across a wide range of peptide sequences, including pharmaceutical and cosmetic peptides.