title: Aryldithioethyloxycarbonyl (Ardec): a new family of amine protecting groups removable under mild reducing conditions and their applications to peptide synthesis.
abstract: The development of phenyldithioethyloxycarbonyl (Phdec) and 2-pyridyldithioethyloxycarbonyl (Pydec) protecting groups, which are thiol-labile urethanes, is described. These new disulfide-based protecting groups were introduced onto the epsilon-amino group of L-lysine; the resulting amino acid derivatives were easily converted into N alpha-Fmoc building blocks suitable for both solid- and solution-phase peptide synthesis. Model dipeptide(Ardec)s were prepared by using classical peptide couplings followed by standard deprotection protocols. They were used to optimize the conditions for complete thiolytic removal of the Ardec groups both in aqueous and organic media. Phdec and Pydec were found to be cleaved within 15 to 30 min under mild reducing conditions: i) by treatment with dithiothreitol or beta-mercaptoethanol in Tris.HCl buffer (pH 8.5-9.0) for deprotection in water and ii) by treatment with beta-mercaptoethanol and 1,8-diazobicyclo[5.4.0]undec-7-ene (DBU) in N-methylpyrrolidinone for deprotection in an organic medium. Successful solid-phase synthesis of hexapeptides Ac-Lys-Asp-Glu-Val-Asp-Lys(Ardec)-NH2 has clearly demonstrated the full orthogonality of these new amino protecting groups with Fmoc and Boc protections. The utility of the Ardec orthogonal deprotection strategy for site-specific chemical modification of peptides bearing several amino groups was illustrated firstly by the preparation of a fluorogenic substrate for caspase-3 protease containing the cyanine dyes Cy 3.0 and Cy 5.0 as FRET donor/acceptor pair, and by solid-phase synthesis of an hexapeptide bearing a single biotin reporter group.
authors.affiliation: IRCOF/LHO, Equipe de Chimie Bio-Organique, UMR 6014 CNRS, INSA de Rouen et Université de Rouen, 1, rue Tesnières, 76131 Mont-Saint-Aignan Cedex, France.
authors.forename: Milaine
authors.initials: M
authors.lastname: Lapeyre
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leprince
authors.forename: Marc
authors.initials: M
authors.lastname: Massonneau
authors.forename: Hassan
authors.initials: H
authors.lastname: Oulyadi
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Renard
authors.forename: Anthony
authors.initials: A
authors.lastname: Romieu
authors.forename: Gerardo
authors.initials: G
authors.lastname: Turcatti
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
mesh_terms: D000588:Amines / Q000737:chemistry*; D001671:Biochemistry / Q000379:methods*; D031541:Fluorescence Resonance Energy Transfer; D008239:Lysine / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis*; D012996:Solutions; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014520:Urethane / Q000737:chemistry
chemical_list: D000588:Amines; D010455:Peptides; D012996:Solutions; D013438:Sulfhydryl Compounds; D014520:Urethane; D008239:Lysine