title: Synthesis and formation of an EMS correlated contaminant in biotechnologically manufactured L-tryptophan.
abstract: Contaminants in biotechnologically manufactured L-Tryptophan (Trp) are suspected to be responsible for the outbreak of an unknown autoimmune disease in 1989. The contaminants, found in Trp-lots of a Japanese manufacturer, are classified in EMS-correlated and non EMS-correlated substances. Up to now six EMS-correlated substances are known. One of these compounds is 2-(3'-indolylmethyl)-indole (IMT). IMT was detected as a major contaminant in two investigated EMS-associated trp-samples. In a seven step chemical synthesis IMT was obtained for use as a reference substance. A model system to investigate the formation of IMT was created using Trp and 3-indolylmethanol (IM). IMT formation was observed at acidic and alkaline pH-values and the optimal molar ratio of Trp to IM is 100:1. In addition an IMT formation was observed from indole, formaldehyde and Trp as well as from Trp and 3-indolylacetaldehyde.
authors.affiliation: Institute for Biochemistry and Food Chemistry, University of Hamburg.
authors.forename: B
authors.initials: B
authors.lastname: Müller
authors.forename: C
authors.initials: C
authors.lastname: Pacholski
authors.forename: T
authors.initials: T
authors.lastname: Simat
authors.forename: H
authors.initials: H
authors.lastname: Steinhart
mesh_terms: D001709:Biotechnology / Q000592:standards; D002851:Chromatography, High Pressure Liquid; D004196:Disease Outbreaks; D004340:Drug Contamination; D016603:Eosinophilia-Myalgia Syndrome / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D007211:Indoles / Q000032:analysis; D007564:Japan / Q000453:epidemiology; D014364:Tryptophan / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000737:chemistry* / Q000592:standards
chemical_list: D007211:Indoles; D014364:Tryptophan