The conjugation of proteins with polyethylene glycol and other polymers

Biochemical modifications of avidin improve pharmacokinetics and biodistribution, and reduce immunogenicity

“…mPEG modification is supposed to provide a protection as a surface barrier to large molecule interaction such as proteolytic enzymes, thus making clearance slower as has already been reported for several proteins (Nucci et al, 1991;Kartre, 1993). The modification with an average of seven mPEG chains appeared to be ideal to raise the plasma clearance of AV to a value (5.8 h) intermediate between those of AV and SA.…”

Reversible PEGylation of peptide YY3‐36 prolongs its inhibition of food intake in mice

“…Covalent attachment of 40 kDa polyethylene glycol (PEG) to proteins and peptides effectively prevents kidney filtration, thereby prolonging the half-life of the resulting conjugates from minutes to many hours [11][12][13][14]. In addition, PEGylation protects the peptides from proteolysis by restricting access to proteases [13,[15][16][17].…”

“…Covalent attachment of PEG to proteins prolongs their half-life in vivo, but often leads to a drastic loss of their biological or pharmacological activity [11][12][13][14][15][16][17][18]. We found that PEGylation of PYY by standard chemistry, i.e., through formation of a stable bond, led to its complete inactivation.…”

Prolonging the Action of Protein and Peptide Drugs by a Novel Approach of Reversible Polyethylene Glycol Modification

“…1 -conjugated therapeutic proteins have been shown to exhibit clinical properties superior to those of their corresponding unmodified parent proteins (1)(2)(3). Apparently, covalent binding of PEG to proteins produces steric interference, protecting conjugates from proteolysis and decreasing their rate of clearance from the circulation system via intracellular uptake and kidney filtration (2,6,7).…”