Functionalized Polyethylene Glycols (PEG’s)

ChemFiles Volume 5 Article 12

Introduction

The chemical modification of biologically active compounds, such as peptides, proteins, antibody fragments, aptamers, enzymes, and small molecules with polyethylene glycol (referred to as “PEGylation”), is an effective method to tailor molecular properties to particular applications. The PEG moiety within such conjugates provides, for example, water solubility, biocompatibility, and flexibility. PEGylation of a therapeutic agent can prolong the half-life of the drug in the circulation, reduce its immunogenicity and antigenicity, prevent biological degradation by reducing proteolysis and finally, alter the pattern of drug distribution.1,2 After the first therapeutic PEG-protein conjugate (PEG-adenosine deaminase, PEG-ADA3) had been approved by the FDA in 1991, a large number of PEG-protein conjugates had been described for therapeutic use against a range of diseases.4,5 PEG-enzyme complexes found application in biotechnology because they increase the solubility, stability, and activity of the enzymes in hydrophobic organic solvents.4,6

Further important applications of functionalized polyethylene glycols:

  • Preparation of graft polymeric supports for Solid-Phase Peptide Synthesis (SPPS)7
  • Introduction of solubilizing handles in SPPS8
  • Soluble polymer supports for Peptide Synthesis9,10
  • Soluble polymer supports for Organic Synthesis11
  • Introduction of hydrophilic amino acids in Peptide Synthesis12
  • Preparation of PEG-ligand conjugates for affinity partitioning of macromolecules13
  • Preparation of PEG-coated surfaces14
  • Linking of macromolecules to surfaces15
  • Synthesis of targetable polymeric drugs16
  • Preparation of PEG-glycoprotein conjugates17
  • Preparation of PEG-cofactor adducts for biorectors18

Sigma-Aldrich offers a broad portfolio of PEG reagents with molecular weights up to 20 kDa for efficient PEGylations. Numerous homobifunctionalized, heterobifunctionalized, and mono-methoxy endcapped monofunctionalized linear PEG’s are available in high quality. We provide polyethylene glycols activated for the most widely used conjugations to primary amines or thiols. The introduction of different protecting groups leads to extremely useful macromolecular cross-linking agents and spacers.

Please take a look at our unique series of monodisperse polyethylene glycols with an oligomer purity of more than 90– 95%. Sigma-Aldrich homo- and heterobifunctional PEG products (n=5-18) with high oligomer purity are superior reagents for drug delivery formulations, affinity labeling, protein engineering, surface modification, combinatorial chemistry, and any product development whenever accuracy and control are essential.

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References

  1. Mehvar, R. Pharm. Pharmaceut. Sci. 2000, 3, 125.
  2. Wang-Yi, L. J.Biochem. Cell Biology 2002, 34, 396.
  3. Levy, J. et al. J. Pediatr. 1988, 113, 312. 
  4. Inada, Y. et al. TIBTECH, 1995, 13, 86. 
  5. Harris, J. M.; Martin, N. E.; Madi, M. Clin. Pharmacokinet. 2001, 40, 539. 
  6. Nakamura, A. et al. J. Biol. Chem. 1986, 261, 16792. 
  7. Zalipski, S. et al. In Peptides: Structure and Function; Deber, C. M., Hruby, V. J., Kopple, K. H., Eds.; Pierce Chemical Co: Rockford, 1985; p 257. 
  8. Seitz, O.; Kunz, H. J. Org. Chem. 1997, 62, 813. 
  9. Mutter, M.; Bayer, E. Angew. Chemie 1974, 86, 101. 
  10. Pillai V. N. R.; Mutter, M. J. Org. Chem. 1980, 45, 5364. 
  11. Gravert, D. J.; Janda, K. D. Chem. Rev. 1997, 97, 489. 
  12. Koskinen, A. M. P. et al. Bioorg. Med. Chem. Lett. 1995, 5, 573. 
  13. Cordes, A.; Kula, M.-R. J. Chromat. 1986, 376, 375. 
  14. Harris, J. M. et al. J. Polym. Sci. Polym. Chem. Ed. 1984, 22, 341. 
  15. Andreadis, J. D.; Chrisey, L. A. Nucleic Acids Res. 2000, 28 (2), e5. 
  16. Zalipski, S.; Barany, G. J. Bioact. Compatible Polym. 1990, 5, 227. 
  17. Urrutigoity, M.; Souppe, J. Biocatalysis 1989, 2, 145. 
  18. Okada, H.; Urabe, I. Meth. Enzymol. 1987, 136, 34.

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