Reubsaet J L, Beijnen J H, Bult A, Hop E, Vermaas R, Kellekule Y, Kettenes-van den Bosch J J, Underberg W J
Faculty of Pharmacy, Universiteit Utrecht, The Netherlands.
Anal Chem. 1995 Dec 1;67(23):4431-6. doi: 10.1021/ac00119a036.
The basic hexapeptide antagonist [Arg6,D-Trp7,9,MePhe8]-substance P (6-11) was degraded in acid and alkaline media. In acid solution, only one degradation product is found whereas in alkaline solution at least six products are formed. These compounds were analytically characterized and structurally identified by reversed-phase high-performance liquid chromatography, capillary electrophoresis, liquid chromatography/mass spectrometry, fast atom bombardment tandem mass spectrometry, optical rotation analysis, and chiral gas chromatography. The product formed in acidic solution is the terminally deamidated antagonist [Arg6,D-Trp7,9,MePhe8]substance P (6-11); this product was also found in alkaline degradation mixtures. Other important degradation products originate from racemization of the amino acid residue L-Met, formation of ornithine from Arg, and the oxidation of Met to its sulfoxide form.
基本的六肽拮抗剂[精氨酸6，D-色氨酸7,9，甲基苯丙氨酸8]-P物质（6-11）在酸性和碱性介质中会发生降解。在酸性溶液中，仅发现一种降解产物，而在碱性溶液中至少会形成六种产物。通过反相高效液相色谱法、毛细管电泳法、液相色谱/质谱法、快原子轰击串联质谱法、旋光分析和手性气相色谱法对这些化合物进行了分析表征和结构鉴定。在酸性溶液中形成的产物是末端脱酰胺化的拮抗剂[精氨酸6，D-色氨酸7,9，甲基苯丙氨酸8]P物质（6-11）；该产物在碱性降解混合物中也被发现。其他重要的降解产物源自氨基酸残基L-蛋氨酸的消旋化、精氨酸形成鸟氨酸以及蛋氨酸氧化为其亚砜形式。
