Since the introduction of solid phase synthesis by Dr. Bruce Merrifield, polystyrene was used as the base matrix.   In the first decades, peptides were short and rarely over 15-20 amino acids. With short and simple peptides, polystyrene resins are the most appropriate because good synthesis efficiency can be achieved at low cost

In the 1980’s, many chemists demonstrated that adding a PEG chain to a polystyrene resin is helping to achieve better crude purities.  But these PS-PEG resins had the following disadvantages:

• Low loading (0.2-0.3 mmol/g)
• Leaching.  The PEG is usually linked to the polystyrene by an acid labile bound which can be lost during the cleavage step. This will affect the purity of the final peptide because PEGs will also precipitate during the precipitation with ether.
• Expensive
• Small production scale

Based on the positive effects of PEG on peptide purity, Matrix Innovation Inc. invested 6 years in  the development of ChemMatrix®, a totally PEG resin.  The structure of the resin was designed to be made only of primary ether bounds to procure the chemical stability required to avoid leaching.  The PEG length and matrix structure was selected to obtain a loading range of 0.6 to 0.7 mmol/g for the aminomehtyl-ChemMatrix® and therefore have a binding capacity comparable to polystyrene.

Over the last years, we have seen a significant increase in the length of peptides.  Synthesis techniques and coupling reagents were improved to increase the crude purity but the selection of the right resin still remains a crucial choice.  Changing to a totally PEG resin will be your best investment to increase the crude purity of your long, complex or hydrophobic peptides.