title: Innovative chemical synthesis and conformational hints on the lipopeptide liraglutide.
abstract: Liraglutide is a new generation lipopeptide drug used for the treatment of type II diabetes. In this work, we describe new approaches for its preparation fully by chemical methods. The key step of these strategies is the synthesis in solution of the Lys/γ-Glu building block, Fmoc-Lys-(Pal-γ-Glu-OtBu)-OH, in which Lys and Glu residues are linked through their side chains and γ-Glu is N(α) -palmitoylated. This dipeptide derivative is then inserted into the peptide sequence on solid phase. As liraglutide is obtained with great purity and high yield, our approach can be particularly attractive for an industrial production. We also report here the results of a circular dichroism conformational analysis in a membrane mimetic environment that offers new insights into the mechanism of action of liraglutide. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Fresenius Kabi Anti-Infectives Srl, 45010, Villadose (RO), Italy.|Institute of Chemistry, St. Petersburg State University, 198504, Petrodvorets, St. Petersburg, Russia.
authors.forename: Ivan
authors.identifier: http://orcid.org/0000-0001-6897-3528
authors.initials: I
authors.lastname: Guryanov
authors.affiliation: Fresenius Kabi Anti-Infectives Srl, 45010, Villadose (RO), Italy.
authors.forename: Alex
authors.initials: A
authors.lastname: Bondesan
authors.affiliation: Fresenius Kabi Anti-Infectives Srl, 45010, Villadose (RO), Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Visentini
authors.affiliation: ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, 35131, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Orlandin
authors.affiliation: ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, 35131, Padova, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Biondi
authors.affiliation: ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, 35131, Padova, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Toniolo
authors.affiliation: ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, 35131, Padova, Italy.
authors.forename: Fernando
authors.initials: F
authors.lastname: Formaggio
authors.affiliation: Fresenius Kabi Anti-Infectives Srl, 45010, Villadose (RO), Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ricci
authors.affiliation: Fresenius Kabi Anti-Infectives Srl, 45010, Villadose (RO), Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Zanon
authors.affiliation: Fresenius Kabi Anti-Infectives Srl, 45010, Villadose (RO), Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Cabri
mesh_terms: D000595:Amino Acid Sequence; D005449:Fluorenes / Q000737:chemistry; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D055666:Lipopeptides / Q000138:chemical synthesis*; D000069450:Liraglutide / Q000138:chemical synthesis*; D008239:Lysine / Q000737:chemistry; D008567:Membranes, Artificial; D010713:Phosphatidylcholines / Q000737:chemistry; D011487:Protein Conformation; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D014270:Trifluoroethanol / Q000737:chemistry
chemical_list: D005449:Fluorenes; D007004:Hypoglycemic Agents; D055666:Lipopeptides; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D012967:Sodium Dodecyl Sulfate; D018698:Glutamic Acid; D014270:Trifluoroethanol; D000069450:Liraglutide; C017251:1,2-oleoylphosphatidylcholine; D008239:Lysine
keywords: circular dichroism; conformational analysis; lipopeptide; liraglutide; peptide synthesis