PEGylation of Proteins: A Structural Approach - Structural properties of PEGylated proteins could play an increasingly important role in developing optimal therapeutic protein drugs. - BioPharm

ADVERTISEMENT

PEGylation of Proteins: A Structural Approach
Structural properties of PEGylated proteins could play an increasingly important role in developing optimal therapeutic protein drugs.


BioPharm International
Volume 19, Issue 4

Although PEGylation remains an excellent choice for protein stabilization and controlled dosage of protein drugs, however, it still poses a number of challenges. Manufacturing costs of goods, PEG polydispersity, drug clearance from the body, and loss of biological activity resulting from PEGylation are just a few of the areas in need of further investigation. Because of the improvement of PEG purification processes, the commercially available PEGs are nowadays less polydisperse, allowing for larger molecular weight polymers to be used. In addition, the use of branched PEGs and the development of robust site specific PEGylation have expanded and will continue to expand the polymer options available for protein PEGylation. Bigger and better PEGs would require better characterization of the overall structural properties of the PEG and the conjugated complex. A conformational approach to PEGylated species equilibrium offers insight into alternative options for optimization of the PEGylation reaction.

A. Sorina Morar, PhD, is a scientist, Process Development, Diosynth Biotechnology, 3000 Weston Parkway, Carey, NC 25713, 919.388.5649, fax: 919.678.0366,

REFERENCES

1. Maggio ET, Ramnarayan K. Recent developments in computational proteomics. Trends Biotechnol. 2001, 19:266-72.

2. Krishnamurthy R, Manning MC. The stability factor: importance in formulation development. Curr. Pharm. Biotechnol. 2002, 3:361-71.

3. Meyer JD, Ho B, Manning MC. Effects of conformation on the chemical stability of pharmaceutically relevant polypeptides. Pharm. Biotechnol. 2002, 13:85-107.

4. Goldberg M, Gomez-Orellana I. Challenges for the oral delivery of macromolecules. Nat. Rev. Drug Discov. 2003, 2:289-95.

5. DeSantis G, Jones JB. Chemical modification of enzymes for enhanced functionality. Curr. Opin. Biotechnol. 1999, 10:324-30.

6. Marshall SA, et al. Rational design and engineering of therapeutic proteins. Drug Discov. Today 2003, 8:212-21.

7. Burnham NL. Polymers for delivering peptides and proteins. Am. J. Hosp. Pharm. 1994, 51:210-18.

8. Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nat. Rev. Drug Discov. 2003, 2:214-21.

9. Heathcote EJ, et al. Peginterferon α-2a in patients with chronic hepatitis C and cirrhosis. N. Engl. J. Med. 2000, 343:1673-80.

10. Harris JM. Poly(ethylene glycol) chemistry: biotechnical and biomedical applications. New York: Plenum; 1992.

11. ACS Symposium series 680. Poly(ethylene glycol) chemistry and biological applications. 1997 ed. Washington, DC: American Chemical Society; 1997.

12. Yamaoka T, Tabata Y, Ikada Y. Distribution and tissue uptake of poly(ethylene glycol) with different molecular weights after intravenous administration to mice. J. Pharm. Sci. 1994, 83:601-06.

13. Zalipsky S. Chemistry of polyethylene glycol conjugates with biologically active molecules. Adv. Drug Deliv. Rev. 1995, 16:157-82.

14. Heymann B, Grubmuller H. Elastic properties of poly(ethylene-glycol) studied by molecular dynamics stretching simulations. Chem. Phys. Lett. 1999, 307:425-32.

15. Tasaki K. Poly(oxyethylene)-water interactions: a molecular dynamics study. J. Am. Chem. Soc. 1996, 118:8459-69.

16. Oesterhelt F, Rief M, Gaub HE. Single molecule force spectroscopy by AFM indicates helical structure of poly(ethylene-glycol) in water. New J. Phys. 1999, 1:6.1-6.11.

17. Wilkins DK, et al. Hydrodynamic radii of native and denatured proteins measured by pulse field gradient NMR techniques. Biochemistry 1999, 38:16424-31.

18. Garcia DLT, Huertas ML, Carrasco B. Calculation of hydrodynamic properties of globular proteins from their atomic-level structure. Biophys. J. 2000, 78:719-30.

19. Bae SC, et al. Single isolated macromolecules at surfaces. Curr. opin. Solid State Mater. Sci. 2001, 5:327-32.

20. Devanand K, Selser JC. Asymptotic behavior and long range interactions in aqueous solutions of poly(ethylene oxide). Macromol. 1991, 24:5943-47.


blog comments powered by Disqus

ADVERTISEMENT

ADVERTISEMENT

USP Awards Analytical Research
August 15, 2014
FDA Warns about Fraudulent Ebola Treatments
August 15, 2014
Guilty Plea to Importing Illegal Cancer Drugs
August 15, 2014
Amgen Recalls Aranesp Prefilled Syringes
August 15, 2014
Report Predicts Generics Production Return to US
August 15, 2014
Author Guidelines
Source: BioPharm International,
Click here