STRUCTURAL IDENTIFICATION OF THE DEGRADATION PRODUCTS OF THE ANTITUMOR PEPTIDE ANTAGONIST [ARG(6),D-TRP(7,9),MEPHE(8)]SUBSTANCE-P(6-11)

The basic hexapeptide antagonist [Arg(6),D-Trp(7,9),MePhe(8)]substance P (6-11) was degraded in acid and alkaline media, In acid solution, o nly one degradation product is found whereas in alkaline solution at l east six products are formed. These compounds were analytically charac terized and structurally identified by reversed-phase highperformance liquid chromatography, capillary electrophoresis, liquid chromatograph y/mass spectrometry, fast atom bombardment tandem mass spectrometry, o ptical rotation analysis, and chiral gas chromatography. The product f ormed in acidic solution is the terminally deamidated antagonist [Arg( 6),D-Trp(7,9),MePhe(8)]substance P (6-11); this product was also found in alkaline degradation mixtures, Other important degradation product s originate from racemization of the amino acid residue L-Met, formati on of ornithine from Arg, and the oxidation of Met to its sulfoxide fo rm.