PEGylation of cyanovirin-N, an entry inhibitor of HIV.
Cyanovirin-N (CV-N) is a potent inhibitor of human immunodeficiency virus and many other viruses. It has a high potential for use as a systemic compound to control viral load or in the development of microbicides to prevent primary viral infection. Due to its cyanobacterial origin it is likely to show the typical drawbacks associated with pharmaceutical use of foreign proteins such as short plasma half-life, proteolysis and immunogenicity. Several strategies were used to covalently bond poly(ethylene glycol) (PEGylate) to CV-N. Random PEGylation at lysine residues resulted in poor retention of antiviral activity. Many site-directed mutants were made to test site-specific PEGylation. One mutant, where glutamine 62 was replaced with cysteine (CV-N(Q62C)) and PEGylated with maleimide activated PEG, retained significant anti-HIV activity in vitro.
Zappe
H
H
Nektar Therapeutics AL Corporation, 490 Discovery Drive, Huntsville, AL 35806, USA. hzappe@nektar.com
Snell
M E
ME
Bossard
M J
MJ
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000737:chemistry* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000737:chemistry* / Q000627:therapeutic use; D004339:Drug Compounding / Q000379:methods; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D008969:Molecular Sequence Data; D011092:Polyethylene Glycols / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; C107733:cyanovirin N; D011092:Polyethylene Glycols