by Michael Pennington
The degree of synthetic difficulty for a peptide sequence depends on several factors: known sequence dependent motifs, incomplete coupling reactions, and limited improvement from recoupling or acetylation (“capping”). This is the result of aggregation of the growing peptide chain due to secondary structure formation during synthesis (i.e., β-sheet formation), interchain or intrachain peptide association via hydrogen bonding or hydrophobic interactions, and peptide-polymer matrix association. This leads to a hindered amino terminus, which results in reduced coupling and deprotection efficiencies. In more ideal reaction conditions, a well-solvated peptide-polymer matrix results in faster and more complete coupling reactions. Traditionally, solid-phase peptide synthesis (SPPS) has been carried out employing cross-linked polystyrene (PS) solid supports. Some of the newer solid supports, such as PEG-PS™ or TentaGel™ resins combine a Peg grafted onto a support (such as polystyrene). These resins have improved had success for difficult peptide sequences due to the enhanced solvation properties of the Peg constituents in preventing aggregation of the peptide on the resin support.
Peptides International also manufactures a fully copolymerized Peg resin. This Cross Linked Ethoxylate Acrylate Resin (CLEARTM) does not possess the hydrophobic polystyrene core of these other Peg-grafted resins. CLEARTM resin incorporates the enhanced hydrophilic properties of the Peg-PS and Tentagel resins due to the chemical properties of the core Ethoxylate Acrylate co-polymer. The resin has superior performance on difficult peptides with either acid or amide C-terminal functionalities. Its hydrophilic properties allow it to even function in aqueous environments allowing for reactions such as solid-phase disulfide oxidation reactions.
We have recently improved the CLEARTM product formulation resulting in a much more mechanically stable resin which performs well in both batch synthesizers with mechanical stirring as well as gas–based mixing. It is “clearly” worth taking a second look at our CLEARTM resins!