Positional Isomers of Monopegylated Interferon α-2a: Isolation, Characterization, and Biological Activity

✍ Scribed by Seth P. Monkarsh; Yuemei Ma; Anthony Aglione; Pascal Bailon; Doreen Ciolek; Barabara Debarbieri; Mary C. Graves; Kurt Hollfelder; Hanspeter Michel; Alicia Palleroni; Jill E. Porter; Emil Russoman; Swapan Roy; Yu-Ching E. Pan

• Publisher: Elsevier Science
• Year: 1997
• Tongue: English
• Weight: 133 KB
• Volume: 247
• Category: Article
• ISSN: 0003-2697
• DOI: 10.1006/abio.1997.2128

✦ Synopsis

ment of Kaposi's sarcoma, chronic hepatitis B, hairy-The success of recombinant interferon a in the clinic cell leukemia, etc. (2, 3). in part is limited by two properties of the protein:

One approach to improve serum half-life, decrease short serum half-life and immunogenicity. To imthe frequency of dosing, and reduce immunogenicity of prove these properties, interferon a-2a was conjugated protein therapeutics is to modify the lysine residues on with polyethylene glycol (PEG-5000). A homogeneous the surface of protein with polyethylene glycol (PEG) preparation of monopegylated interferon a-2a was through a covalent linkage (4). Based on successful subjected to vigorous analytical and activity characclinical trials, PEG-adenosine deaminase and PEGterization. A newly developed ampholyte-free chromaasparaginase have been approved in the United States tofocussing-like cation-exchange HPLC method utilizfor the treatment of adenosine deaminase deficiency ing a sulfopropyl resin was used to separate the (5) and acute lymphoblastic leukemia (6), respectively. monopegylated protein into 11 species. Peptide map-This approach was also used to generate new modified ping, sequencing, and mass spectrometric analyses in-IFN molecules which could be examined for improved dicated that these species are positional isomers therapeutic efficacy.