Oxidation of tryptophan to oxindolylalanine by dimethyl sulfoxide-hydrochloric acid. Selective modification of tryptophan containing peptides.
Tryptophan is readily oxidized to oxindolylalanine (2-hydroxytryptophan) in good yield on treatment in acetic acid solution with a mixture of dimethyl sulfoxide (DMSO) and concentrated aqueous HCl at room temperature. Other sulfoxides can be used in combination with HCl; for example, methionine sulfoxide reacts with an equimolar amount of tryptophan to give high yields of methionine and oxindolylalanine. Methionine and cysteine are quantitatively oxidized by DMSO/HCl to methionine sulfoxide and cystine, respectively. The tryptophan containing peptides LRF (luteinizing hormone-releasing factor), somatostatin, valine-gramicidin A and ACTH 1-24 were each treated with the DMSO/HCl reagent in acetic acid solution and the corresponding oxindolylalanine-derivatives isolated in over 90% yield after chromatography. The identity and purity of the derivatives were established on the basis of ultraviolet spectral characteristics and quantitative amino acid analysis of the oxindolylalanine content of acid hydrolyzates of the oxidized peptides with 3N-p-toluenesulfonic acid at 110 degrees for 24 h. The results indicate that modification of tryptophan peptides with DMSO/HCl provides a useful procedure, which seems superior to previously used reagents. In addition, the method could be well applied to other indoles of biological and pharmacological interest.
D006916:5-Hydroxytryptophan / Q000138:chemical synthesis*; D000324:Adrenocorticotropic Hormone / Q000032:analysis; D000596:Amino Acids / Q000032:analysis; D055598:Chemical Phenomena; D002621:Chemistry; D004121:Dimethyl Sulfoxide; D007987:Gonadotropin-Releasing Hormone / Q000032:analysis; D006096:Gramicidin / Q000032:analysis; D006851:Hydrochloric Acid; D010084:Oxidation-Reduction; D010446:Peptide Fragments; D013004:Somatostatin / Q000032:analysis; D014364:Tryptophan
D000596:Amino Acids; D010446:Peptide Fragments; D006096:Gramicidin; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; D014364:Tryptophan; D000324:Adrenocorticotropic Hormone; D006916:5-Hydroxytryptophan; D006851:Hydrochloric Acid; D004121:Dimethyl Sulfoxide