title: C-Terminally PEGylated hGH-derivatives.
abstract: A two-step strategy was used for the preparation of C-terminally PEGylated hGH-derivatives. In a first step a CPY-catalyzed transpeptidation was performed on hGH-Leu-Ala, introducing reaction handles, which were used in the second step for the ligation of PEG-moieties. Both oxime-ligation and copper(I) catalyzed [2+3]-cycloaddition reactions were used for the attachment of PEG-moieties. The biological data show a dependency of the potency of the hGH-derivatives on both size as well as shape of the PEG-group.
authors.affiliation: Protein Engineering, Novo Nordisk A/S, Novo Nordisk Park, 2760 Maaloev, Denmark. bpes@novonordisk.com
authors.forename: Bernd
authors.initials: B
authors.lastname: Peschke
authors.forename: Magali
authors.initials: M
authors.lastname: Zundel
authors.forename: Sonja
authors.initials: S
authors.lastname: Bak
authors.forename: Trine R
authors.initials: TR
authors.lastname: Clausen
authors.forename: Niels
authors.initials: N
authors.lastname: Blume
authors.forename: Anja
authors.initials: A
authors.lastname: Pedersen
authors.forename: Florencio
authors.initials: F
authors.lastname: Zaragoza
authors.forename: Kjeld
authors.initials: K
authors.lastname: Madsen
mesh_terms: D053801:Capillary Electrochromatography; D002851:Chromatography, High Pressure Liquid; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D011986:Receptors, Somatotropin / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet
chemical_list: D007202:Indicators and Reagents; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D011092:Polyethylene Glycols