Polyethylene glycol-protein conjugates

Ladd D, Gregg C. Mono-N-terminal polyethylene glycol)-protein conjugates. Adv. Drug Deliv. Rev. 2002 54 477-485. 

Bolon B, Faust J, Storm N, et al. Cytoplasmic vacuoles in renal tubular epithelium of mice given polyethylene glycol (PEG)-conjugated proteins are reduced by alternating PEG size and conformation. Tox Sci 2001 60(1) 376. 

A promising method for reducing allergenicity relies on the polymerization of proteins with polyethylene glycol (PEG). Conjugation of whey proteins with nontoxic... 

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. 

N. Katre, The conjugation of proteins with polyethylene glycol and other polymers. Altering properties of proteins to enhance their therapeutic potential. Advances Drug Del. Rev, 10, 91 (1993). 

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. 

Zalipsky, S., Seltzer, R., and Nho, K. (1991) Succinimidyl carbonates of polyethylene glycol Useful reactive polymers for preparation of protein conjugates. In Polymeric Drugs and Drug Delivery Systems (R.L. Dunn, and R.M. Ottenbrite, eds.), pp. 91-100. American Chemical Society, Washington, D.C. 

Parveen S, Sahoo SK. Nanomedicine clinical applications of polyethylene glycol conjugated proteins and drugs. Clin Pharmacokinet 2006 45 966-88. 

Bendele A, Seely J, Richey C, et al. Short communication renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated protein. Tox Sci 1998 42 152. 

Lipid moieties coupled to polyethylene glycol (PEG) have been used to increase the blood circulation time of lipoplexes (Fig. 32). The PEG-lipid conjugates such as DOPE-PEG, Chol-PEG, ceramides-PEG and their derivatives are then coformulated with the cationic lipid, helper lipid, and DNA. This results in coating the surface of the lipoplexes with PEG and preventing undesired association with plasma proteins or circulating cells (stealth liposomes). Recently, a-tocopheryl PEG-succinate (TPGS) was also used in gene delivery formulations because of its ability to confer not only a stealth property but also antioxidant and absorption enhancer properties [129]. 

Wroblewska, B. and Jgdrychowski, L. 2002b. Effect of conjugation of cow milk whey proteins with polyethylene glycol on changes in their immunoreactive and allergic properties. Food Agric Immunol 14 155-162. 

---