title: The first "ready-to-use" benzene-based heterotrifunctional cross-linker for multiple bioconjugation.
abstract: The synthesis and applications of the first water-soluble benzene derivative bearing a set of three different and orthogonal bioconjugatable groups (aminooxy, azido and thiol) are described. The combined use of a 5-amino isophthalic acid scaffold and unusual acid-labile protecting groups for temporarily masking aminooxy and thiol moieties has enabled the development of a highly convergent approach towards the synthesis of such a trivalent bioconjugation platform in good yields. The potential utility of this "ready-to-use" cross-linking reagent for creating complex and fragile tri-component (bio)molecular systems was illustrated through (1) the rapid preparation of a three-colour FRET cascade with valuable spectral properties and (2) the luminescent/fluorescent labelling of peptides and peptide-oligonucleotide conjugates. Thus, such (bio)molecular assemblies were readily obtained via a three-step process or in a "one-pot" manner, both involving oxime ligation, thiol-alkylation (S(N)2 or Michael addition) and copper-catalysed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reactions.
authors.affiliation: Normandie Univ, COBRA, UMR 6014 & FR 3038, UNIV Rouen, INSA Rouen, CNRS, 1 Rue Tesnières, 76821 Mont St Aignan Cedex, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Viault
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dautrey
authors.forename: Nicolas
authors.initials: N
authors.lastname: Maindron
authors.forename: Julie
authors.initials: J
authors.lastname: Hardouin
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Renard
authors.forename: Anthony
authors.initials: A
authors.lastname: Romieu
mesh_terms: D001386:Azides / Q000138:chemical synthesis / Q000737:chemistry; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D049408:Luminescent Agents / Q000138:chemical synthesis* / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D001386:Azides; D001555:Benzene Derivatives; D003432:Cross-Linking Reagents; D049408:Luminescent Agents; D009841:Oligonucleotides; D010455:Peptides; D013438:Sulfhydryl Compounds