Spontaneous chemical degradation of substance P in the solid phase and in solution

The instability of the undecapeptide substance P (SP), a neuropeptide implicated in several physiological processes, was occasionally observed when the peptide was stored in the solid state or in solution. The aim of the present study was to identify the decomposition products of SP stored as lyophilized peptide or in aqueous neutral solution. The main pathway of the decomposition of SP acetate consists of the subsequent release of N-terminal dipeptides via their diketopiperazines, cyclo(Arg-Pro) and cyclo(Lys-Pro). In contrast to the decomposition of the acetate of SP, the hydrochloride and trifluoroacetate salts were found to be considerably more stable. Under the studied conditions the release of N-terminal dipeptides dominates over other possible routes of spontaneous modifications, such as S-oxidation and deamidation.