PEGylation, successful approach to drug delivery.

PEGylation defines the modification of a protein, peptide or non-peptide molecule by the linking of one or more polyethylene glycol (PEG) chains. This polymer is non-toxic, non-immunogenic, non-antigenic, highly soluble in water and FDA approved. The PEG-drug conjugates have several advantages: a prolonged residence in body, a decreased degradation by metabolic enzymes and a reduction or elimination of protein immunogenicity. Thanks to these favorable properties, PEGylation now plays an important role in drug delivery, enhancing the potentials of peptides and proteins as therapeutic agents.

[1]  PEGylated Proteins as Cancer Therapeutics , 2006 .

[2]  J. Eaton,et al.  Structural and functional consequences of antigenic modulation of red blood cells with methoxypoly(ethylene glycol). , 1999, Blood.

[3]  J. Kopeček,et al.  Polymers containing enzymatically degradable bonds, 7. Design of oligopeptide side-chains in poly[N-(2-hydroxypropyl)methacrylamide] copolymers to promote efficient degradation by lysosomal enzymes† , 1983 .

[4]  D. Wyss,et al.  Structural and biological characterization of pegylated recombinant interferon alpha-2b and its therapeutic implications. , 2002, Advanced drug delivery reviews.

[5]  S. W. Kim,et al.  Effects of PEG conjugation on insulin properties. , 2002, Advanced drug delivery reviews.

[6]  K. Ulbrich,et al.  Polymers containing enzymatically degradable bonds V. Hydrophilic polymers degradable by papain. , 1980, Biomaterials.

[7]  V. Erdmann,et al.  Automated incorporation of polyethylene glycol into synthetic oligonucleotides , 1993 .

[8]  J. Kopeček,et al.  Development of N-(2-Hydroxypropyl)Methacrylamide Copolymers as Carriers of Therapeutic Agents , 1983 .

[9]  F. Veronese,et al.  Protein, peptide and non-peptide drug PEGylation for therapeutic application , 2004 .

[10]  Mariangela Spitali,et al.  Therapeutic antibody fragments with prolonged in vivo half-lives , 1999, Nature Biotechnology.

[11]  Shan S. Wong,et al.  Chemistry of Protein Conjugation and Cross Linking , 1991 .

[12]  P. Caliceti,et al.  Active Site Protection of Proteolytic Enzymes by Poly(ethylene glycol) Surface Modification , 1993 .

[13]  C. Langer.  CT-2103: a novel macromolecular taxane with potential advantages compared with conventional taxanes. , 2004, Clinical lung cancer.

[14]  F. Davis,et al.  Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. , 1977, The Journal of biological chemistry.

[15]  A. Helenius,et al.  Essentials of Glycobiology, A. Varki, R. Cummings, J. Esko, H. Freeze, G. Hart, J. Marth. Cold Spring Harbor Laboratory Press, Cold Spring Harbor NY (1999), 668 pp. $95.00 , 2000 .

[16]  J. Svanvik,et al.  Hepatic excretion and metabolism of polyethylene glycols and mannitol in the cat. , 1993, Journal of hepatology.

[17]  A. Shilatifard,et al.  Posttranslational modifications of histones by methylation. , 2004, Advances in protein chemistry.

[18]  F. Veronese,et al.  Selective Alkylation and Acylation of α and ε Amino Groups with PEG in a Somatostatin Analogue: Tailored Chemistry for Optimized Bioconjugates , 2002 .

[19]  F. Veronese,et al.  Anchimeric assistance effect on regioselective hydrolysis of branched PEGs: a mechanistic investigation. , 2004, Bioorganic & medicinal chemistry.

[20]  Yasuo Yoshioka,et al.  Optimal site-specific PEGylation of mutant TNF-α improves its antitumor potency , 2004 .

[21]  F. Veronese,et al.  Highly efficient technetium-99m labeling procedure based on the conjugation of N-[N-(3-diphenylphosphinopropionyl)glycyl]cysteine ligand with poly(ethylene glycol). , 2004, Bioconjugate chemistry.

[22]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[23]  J. A. Scarlett,et al.  Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. , 2000, The New England journal of medicine.

[24]  R. Rodnight.  Protein Kinases and Phosphatases , 1983 .

[25]  P. Caliceti,et al.  Synthesis of the conjugate of superoxide dismutase with the copolymer of divinyl ether and maleic anhydride retaining enzymatic activity , 1994 .

[26]  M. S. Tewart,et al.  Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. , 2000 .

[27]  F. Davis,et al.  Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. , 1977, The Journal of biological chemistry.

[28]  H. Sato,et al.  Enzymatic procedure for site-specific pegylation of proteins. , 2002, Advanced drug delivery reviews.

[29]  F. Kratz,et al.  Drug-polymer conjugates containing acid-cleavable bonds. , 1999, Critical reviews in therapeutic drug carrier systems.

[30]  Chun Xing Li,et al.  Poly(ethylene glycol)-conjugated anti-EGF receptor antibody C225 with radiometal chelator attached to the termini of polymer chains. , 2001, Bioconjugate chemistry.

[31]  G Waksman,et al.  The biology and enzymology of protein N-myristoylation. , 2001, The Journal of biological chemistry.

[32]  Lawrence A. Yannuzzi,et al.  PRECLINICAL AND PHASE 1A CLINICAL EVALUATION OF AN ANTI-VEGF PEGYLATED APTAMER (EYE001) FOR THE TREATMENT OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION , 2002, Retina.

[33]  M. Royzen,et al.  Anticancer drug delivery systems: multi-loaded N4-acyl poly(ethylene glycol) prodrugs of ara-C. II. Efficacy in ascites and solid tumors. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Y. Yoshioka,et al.  Functionalization of Tumor Necrosis Factor-α Using Phage Display Technique and PEGylation Improves Its Antitumor Therapeutic Window , 2004, Clinical Cancer Research.

[35]  M. Graham.  Pegaspargase: a review of clinical studies. , 2003, Advanced drug delivery reviews.

[36]  Y. Yoshioka,et al.  Optimal site-specific PEGylation of mutant TNF-alpha improves its antitumor potency. , 2004, Biochemical and biophysical research communications.

[37]  V. L. Rath,et al.  Strategies for drug discovery by targeting sulfation pathways. , 2004, Drug discovery today.

[38]  F. Veronese,et al.  Novel monodisperse PEG-dendrons as new tools for targeted drug delivery: synthesis, characterization and cellular uptake. , 2006, Biomacromolecules.

[39]  M. Scott,et al.  Beyond the red cell: pegylation of other blood cells and tissues. , 2004, Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine.

[40]  F. Kawai,et al.  Microbial degradation of polyethers , 2001, Applied Microbiology and Biotechnology.

[41]  D. Filpula,et al.  Controlled release of proteins from their poly(ethylene glycol) conjugates: drug delivery systems employing 1,6-elimination. , 2003, Bioconjugate chemistry.

[42]  P. Bunn.  Early-stage non-small-cell lung cancer: current perspectives in combined-modality therapy. , 2004, Clinical lung cancer.

[43]  D. Brems,et al.  Characterization and Stability of N-terminally PEGylated rhG-CSF , 1996, Pharmaceutical Research.

[44]  M. Hershfield,et al.  Adenosine deaminase deficiency with late onset of recurrent infections: response to treatment with polyethylene glycol-modified adenosine deaminase. , 1988, The Journal of pediatrics.

[45]  Zhi-xin Xu,et al.  Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C. , 2001, Bioconjugate chemistry.

[46]  T. Hunter,et al.  Protein kinases and phosphatases: The Yin and Yang of protein phosphorylation and signaling , 1995, Cell.

[47]  C. Conover,et al.  Poly(ethylene glycol) conjugated drugs and prodrugs: a comprehensive review. , 2000, Critical reviews in therapeutic drug carrier systems.

[48]  W. Bentley,et al.  Nature-Inspired Creation of Protein−Polysaccharide Conjugate and Its Subsequent Assembly onto a Patterned Surface , 2003 .