Polyethylene glycol modifications

Yang B-B, Lum PK, Hayashi MM, Roskos LK. Polyethylene glycol modification of filgrastim results in decreased renal clearance of the protein in rats. J. Pharm. Sci. 2004 93 1367-1373. 

Polyethylene glycol modification prolongs the circulating half-life of proteins. Adapted from [34],... 

H. Tsubery, M. Mironchik, M. Fridkin, Y. Shechter, Prolonging the action of protein and peptide drugs by a novel approach of reversible polyethylene glycol modification. J. Biol. 

Formulation strategies for stabilization of proteins commonly include additives such as other proteins (e.g., serum albumin), amino acids, and surfactants to minimize adsorption to surfaces. Modification of protein structure to enhance stability by genetic engineering may also be feasible, as well as chemical modification such as formation of a conjugate with polyethylene glycol. 

The improvement of its activity and stability has been approach by the use of GE tools (see Refs. [398] and [399], respectively). A process drawback is the fact that the oxidation of hydrophobic compounds in an organic solvent becomes limited by substrate partition between the active site of the enzyme and the bulk solvent [398], To provide the biocatalyst soluble with a hydrophobic active site access, keeping its solubility in organic solvents, a double chemical modification on horse heart cytochrome c has been performed [400,401], First, to increase the active-site hydrophobicity, a methyl esterification on the heme propionates was performed. Then, polyethylene glycol (PEG) was used for a surface modification of the protein, yielding a protein-polymer conjugates that are soluble in organic solvents. 

Several of these problems can be solved by polyplex modification with polyethylene glycol (PEG). PEGylation has been broadly explored for surface shielding ( stealthing ) of many liposomal and nanoparticulate carriers. In the case of cationic polymers, Plank et al. [62] demonstrated that complement activation can be reduced when the polymers are PEGylated. Such a modification can be... 

Protein Modification with Activated Polyethylene Glycols... 

Gotoh, Y., Tsukada, M., and Minoura, N. (1993) Chemical modification of silk fibroin with cyanuric chloride-activated polyethylene glycol Analysis of reaction site by 1H-NMR spectroscopy and conformation of the conjugates. Bioconjugate Cbem. 4, 554-559. 

Clauspol [Claus polyethylene glycol] A variation on the Claus process for removing hydrogen sulfide from gas streams, in which the tail gases are scrubbed with polyethylene glycol to remove residual sulfur dioxide. Clauspol 150 is a modification of this. Developed by the Institut Frangais du Petrole. 

Chemical modification, particularly succinylation, or coupling to polyglycols, can also increase the plasma half-life of enzymes. Conjugation with polyethylene glycol [PEG H(OCH2CH2)nOH] has successfully been employed to stabilize and protect several therapeutic enzymes. Such modification, for example, increases the plasma half-life of superoxide dismutase from 5 h to over 30 h. PEG-coupled asparaginase was approved for general medical use by the FDA in 1994. 

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