Investigation of the triazolinedione (TAD) reaction with tryptophan as a direct route to copolypeptide conjugation and cross-linking

The reaction of tryptophan containing N-carboxyanhydride (NCA) derived polypeptides with triazolinedione (TAD) is demonstrated. This click-like reaction is fast, selective and permits polypeptide conjugation utilising a natural amino acid. It thereby omits the need for synthesis of non-natural amino acid derivatives or protection/deprotection strategies. Its feasibility is demonstrated for the synthesis of polypeptide gels and films using difunctional TAD derivatives such as novel PEG-bis-TAD.