title: Toward solid-phase peptide fragment ligation by a traceless-Ugi multicomponent reaction approach.
abstract: A new methodology to couple peptide fragments on solid support using a traceless isocyanide-based multicomponent reaction is described. The approach uses a microwave-assisted on-resin Ugi four-component reaction to attach a carboxyl free peptide to a supported peptide bearing a free N-terminal amine via the formation of an N-protected amide bond at the ligation site. Afterward, the generated backbone amide protecting group can be efficiently removed by microwave-assisted acidolysis with trifluoroacetic acid to afford a fully deprotected peptide. This straightforward Ugi reaction/deprotection approach was applied to condense various fragment lengths and provided a variety of oligopeptides.
authors.affiliation: Faculty of Pharmacy, Université Laval and Laboratory of Medicinal Chemistry, Centre de recherche du Centre Hospitalier Universitaire de Québec, Québec (QC) G1V 4G2, Canada. eric.biron@pha.ulaval.ca.
authors.forename: Steve
authors.initials: S
authors.lastname: Jobin
authors.affiliation: Faculty of Pharmacy, Université Laval and Laboratory of Medicinal Chemistry, Centre de recherche du Centre Hospitalier Universitaire de Québec, Québec (QC) G1V 4G2, Canada. eric.biron@pha.ulaval.ca.
authors.forename: Alexia
authors.initials: A
authors.lastname: Méjean
authors.affiliation: Faculty of Pharmacy, Université Laval and Laboratory of Medicinal Chemistry, Centre de recherche du Centre Hospitalier Universitaire de Québec, Québec (QC) G1V 4G2, Canada. eric.biron@pha.ulaval.ca.
authors.forename: Sindy-Marcela
authors.initials: SM
authors.lastname: Galindo
authors.affiliation: Faculty of Pharmacy, Université Laval and Laboratory of Medicinal Chemistry, Centre de recherche du Centre Hospitalier Universitaire de Québec, Québec (QC) G1V 4G2, Canada. eric.biron@pha.ulaval.ca.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Liang
authors.affiliation: Faculty of Pharmacy, Université Laval and Laboratory of Medicinal Chemistry, Centre de recherche du Centre Hospitalier Universitaire de Québec, Québec (QC) G1V 4G2, Canada. eric.biron@pha.ulaval.ca.
authors.forename: Simon
authors.initials: S
authors.lastname: Vézina-Dawod
authors.affiliation: Faculty of Pharmacy, Université Laval and Laboratory of Medicinal Chemistry, Centre de recherche du Centre Hospitalier Universitaire de Québec, Québec (QC) G1V 4G2, Canada. eric.biron@pha.ulaval.ca.
authors.forename: Eric
authors.initials: E
authors.lastname: Biron
mesh_terms: D000595:Amino Acid Sequence; D008872:Microwaves; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*
chemical_list: D010446:Peptide Fragments