Mono-N-terminal poly(ethylene glycol)-protein conjugates.
A site-directed method of joining proteins to poly(ethylene glycol) is presented which allows for the preparation of essentially homogeneous PEG-protein derivatives with a single PEG chain conjugated to the amine terminus of the protein. This selectivity is achieved by conducting the reductive alkylation of proteins with PEG-aldehydes at lower pH. Working examples demonstrating the application of this method to improve the delivery characteristics and therapeutic value of several proteins are provided.
Kinstler
Olaf
O
Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1789, USA. okinstle@amgen.com
Molineux
Graham
G
Treuheit
Michael
M
Ladd
David
D
Gegg
Colin
C
D000478:Alkylation; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016297:Mutagenesis, Site-Directed; D011092:Polyethylene Glycols / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D013926:Thrombopoietin / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology
D004337:Drug Carriers; D011506:Proteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin