PolyTherics has shown that disulfide bonds can be made more stable through the addition of a chemical bridge which does not compromise the tertiary structure of the protein. This property has made it possible to exploit the conjugating thiol selectivity of the two sulfurs comprising a disulfide bond and create a bridge for the site-specific attachment of PEG.

Since disulfide bonds occur naturally in the structure of most proteins, TheraPEG ™ technology avoids any artificial engineering to introduce cysteine residues for PEG attachment.

The process by which the chemical bridge is attached is equilibrium-driven and in contrast to other PEGylation methods, distinct, in that none of the reagents used undergo competitive reaction with either amine groups or water. This enables the entire TheraPEG ™ process to be more readily controlled. Furthermore, the bridging moiety imposes no limitation on the size of PEG molecule that can be accommondated within the protein structure; PEG up to 30 kDa in molecular weight, in either linear or branched form, has been successfully validated using the PolyTherics approach.