title: Synthesis of a dicarba analogue of human β-defensin-1 using a combined ring closing metathesis--native chemical ligation strategy.
abstract: We herein describe the first synthesis of the native antimicrobial protein HBD-1 making use of an orthogonal thiol protection strategy and a novel dicarba analogue thereof. The robust hydrocarbon linkage was installed by replacement of one disulfide bond using on-resin ring closing metathesis. The unprecedented 59-membered C-terminal cysteine macrocyclic fragment thus formed then engages in native chemical ligation allowing convergent access to this unique synthetic protein analogue.
authors.affiliation: School of Chemical Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Heapy
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Williams
authors.forename: John D
authors.initials: JD
authors.lastname: Fraser
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Brimble
mesh_terms: D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D023083:beta-Defensins / Q000737:chemistry*
chemical_list: C406407:DEFB1 protein, human; D004220:Disulfides; D023083:beta-Defensins