Peptide resin beads, swelling

The good swelling properties of a peptide resin not only determines its diffusion properties, and therefore the kinetics of a solid-phase reaction,P 9 but also are a requirement for ensuring a uniform distribution of the growing peptide chains throughout the polymeric support. This uniform distribution can actually be achieved, at least in favorable cases, as was shown by an elegant experiment performed by Sarin et al.t where Boc-PH]valine was incorporated into a peptide synthesis and autoradiographs of cross sections of peptide resin beads showed a completely uniform pattern. 

Most of the resins used in batch synthesis are derivatives of 1% crosslinked copoly-(styrene-divinylbenzene) resin in the form of beads 50 to 100 p in diameter. These beads swell four to six times their dry volume in the solvents used in peptide assembly and during the chain elongation process the resin again may double its swollen volume. In batch synthesis, provided the proper size vessel is chosen, the increase in swollen volume is not a major concern. 

Polystyrene resin, frequently used resin material for solid-phase peptide synthesis (SPPS). The polymeric support for SPPS must be chemically inert, mechanically stable, completely insoluble in the solvents used, and easily separated by filtration. For many applications a copolymer of polystyrene with 1% of divinyl benzene as crosslinker is used. The dry resin beads are able to swell up to the five-or sixfold volume in the different organic solvents mainly used for peptide synthesis (e.g., dichloromethane or dimethylfor-mamide). For SPPS the resin material must be chemically functionalized in order to allow for attachment of a handle/liker (e.g. Wang resin), or the first amino acid (—> Merrifield resin). Hydrophilic tentacle polymers gels (TentaGel) are obtained by grafting polyethylene glycol (PEG) chains with an arbitrary degree of polymerization onto porous polystyrene beads. 

Cross-linked polystyrene (PS)-based resins are most commonly used for routine SPPS. Beads of 200 to 400 mesh size distribution (corresponding to a diameter of about 50 pm) and a loading of 0.5 to 0.8 mmol/g present good characteristics for polymer swelling in solvents such as DMF and DCM, diffusion of reactants into the polymer matrix, and accessibility of linker sites buried into the bead. For larger peptides (more than 25 amino acids) or more difficult sequences, a lower loading is required (0.1-0.2 mmol/g). 

Two polymeric supports have classically been nsed in batchwise SPPS. The first is polystyrene polymer cross-linked with 1% of 1,3-divinyl benzene. A typical dry bead has a diameter of 50 fj,m that swells five- to sixfold in DCM or DMF (144). The second was developed on the basis of the idea that the polymeric backbone should be of similar chemical composition, a polyamide, as the peptide backbone (11). Thns, copol5nnerized dimethylacrylamide, ATjAT -bisacryloylethylenediamine, and acryloylsarcosine methyl ester, or polyamide resin, was developed (146). Polyamide snpports are commercially known as Pepsyn resin. Many other supports have been developed that are compatible with batchwise SPPS and are summarized in the more comprehensive reviews (7,10-20,109). 

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