C-Terminally PEGylated hGH-derivatives.
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.
Peschke
Bernd
B
Protein Engineering, Novo Nordisk A/S, Novo Nordisk Park, 2760 Maaloev, Denmark. bpes@novonordisk.com
Zundel
Magali
M
Bak
Sonja
S
Clausen
Trine R
TR
Blume
Niels
N
Pedersen
Anja
A
Zaragoza
Florencio
F
Madsen
Kjeld
K
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
D007202:Indicators and Reagents; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D011092:Polyethylene Glycols