title: An important side reaction using the thiol, 3,6-dioxa-1,8-octanedithiol (DODT), in 9-fluorenylmethoxycarbonyl-based solid phase peptide synthesis.
abstract: A considerable quantity of an alkylation by-product is observed when using 3,6-dioxa-1,8-octanedithiol as a scavenger during acidic release of peptides containing the thioether amino acid methionine from the solid support. Adjustment of the cleavage conditions by replacement of 3,6-dioxa-1,8-octanedithiol with ethane dithiol or by using methionine sulfoxide as an alternative to methionine resulted in no such impurity. The by-product was detectable by liquid chromatography and mass spectrometry and characterised by NMR spectroscopy of an isolated model peptide. It could be effectively removed in a separate post cleavage step by treatment with dilute aqueous acid at 37 °C.
authors.affiliation: School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland, 1142, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Paul W R
authors.initials: PW
authors.lastname: Harris
authors.forename: Renata
authors.initials: R
authors.lastname: Kowalczyk
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Yang
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Williams
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Brimble
mesh_terms: D005019:Ethyl Ethers / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry*; D013058:Mass Spectrometry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: C471080:3,6-dioxa-1,8-octanedithiol; C496789:9-fluorenylmethoxycarbonyl; D005019:Ethyl Ethers; D005449:Fluorenes; D013438:Sulfhydryl Compounds
keywords: 3,6-dioxa-1,8-ocatanedithiol; alkylation; methionine; peptide cleavage