Transcript Protein Modifications

Protein Modifications
-- to increase stability
Goal of protein modification
• Improved bioavailability, including longer
circulation time and slower clearance
• Optimized pharmacokinetics resulting in
sustained duration
• Improved safety profile with lower toxicity,
immunogenicity, and antigenicity
• Increased efficacy
• Decreased dosing frequency
• Improved drug solubility and stability
• Reduced proteolysis
• Controlled drug release
In an aqueous medium, the long, chain-like PEG molecule is heavily hydrated
and in rapid motion. This rapid motion causes the PEG to sweep out a large
volume and prevents the approach and interference of other molecules. As a
result, when attached to a drug, PEG polymer chains can protect the drug
molecules from immune response and other clearance mechanisms,
sustaining drug bioavailability
http://www.nektar.com/wt/page/advanced_pegylation
http://www.peg-drug.com/index.html
Four-Armed Functional PEG
Eight-Arm Functional PEG
Comb-Shaped Copolymers
Chemistry for peptide and protein PEGylation
* M.J. Roberts , M.D. Bentley, J.M. Harris
Advanced Drug Delivery Reviews 54 (2002) 459–476
PEG-proteins: Reaction engineering and separation issues
Conan J. Feea,., James M. Van Alstineb
Chemical Engineering Science 61 (2006) 924 – 939
Neoglycosylation
Alkoxyamine-mediated neoglycosylation