Macromolecules PEGylation

Anytime the term process chemist is used, it usually relates to the development of a small synthetic molecule. However, there has been a growth explosion in the development of macromolecules as of late. These may include proteins, small molecules attached to proteins, pegylated proteins, DNA and RNA fragments, oligonucleotides, monoclonal antibodies, and even personalized medicines in vaccines being made from a specific patient to treat the same patient. As this is a growing trend within the pharmaceutical industry, the term process chemist should include development chemists who are involved in all of the above-mentioned areas. A major difference between these areas and the development of small molecules is that the process to manufacture these complex products usually defines the product versus the other way around for small molecules, where the product defines the process. 

The following is a summary of some of the major points of PEGylation chemistry of biological macromolecules. 

Characterization and control of biological macromolecules requires a variety of analytical tools for detection of chemical and structural modifications. Attachment of a PEG moiety to the biomolecule results in an additional layer of complexity and often requires a unique set of analytical tools to ensure quality and control. In developing PEGylated biomolecules, three key attributes must be controlled to achieve the desired product PEG reagent quality, PEGylation chemistry and stability of the PEG moiety post conjugation. Each of these is described in detail in the following sections. 

Hong SW, Ahn C-H, Huh J, Jo WH (2006) Synthesis of a PEGylated polymeric pH sensor and its pH sensitivity by fluorescence resonance energy transfer. Macromolecules 39 7694... 

The attachment of PEG to bioactive macromolecules is called PEGylation and provides various benefits [312]. These include better water solubility, enhanced resistance to proteolysis, decrease of immimogenicity, antigenicity, toxicity of drugs and slower rate of kidney clearance [313]. PEG has been approved for use in drugs, food and cosmetics [314]. The monodispersity of todays available PEGs eliminates former risks that were related to impurities foimd during chemical synthesis of PEG. 

---