title: Addition of HOBt improves the conversion of thioester-Amine chemical ligation.
abstract: The syntheses of large peptides and of those containing non-natural amino acids can be facilitated by the application of convergent approaches, dissecting the native sequence into segments connected through a ligation reaction. We describe an improvement of the ligation protocol used to prepare peptides and proteins without cysteine residues at the ligation junction. We have found that the addition of HOBt to the ligation, improves the conversion of the ligation reaction without affecting the epimerization rate or chemoselectivity, and it can be efficiently used with peptides containing phosphorylated amino acids.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028, Barcelona, Spain.
authors.forename: Toni
authors.initials: T
authors.lastname: Todorovski
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Suñol
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028, Barcelona, Spain.|Departament de Química Orgànica, University of Barcelona, Martí i Franquès, 1, Barcelona, 08028, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Riera
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028, Barcelona, Spain.|Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys, Barcelona, 23 08010, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Macias
mesh_terms: D000588:Amines / Q000737:chemistry*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D004952:Esters / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000588:Amines; D000596:Amino Acids; D004952:Esters; D010455:Peptides; D013438:Sulfhydryl Compounds; D014230:Triazoles; C011852:1-hydroxybenzotriazole
keywords: cysteine-free native chemical ligation; formation of highly reactive HOBt esters; ligation of peptide fragments through direct aminolysis; native chemical ligation with β-branched residues at ligation junction