Properties of solid supports.
Many supports including composite materials and functionalized surfaces are available for solid-phase synthesis. In the process of selecting the proper support it is important to consider the optimal performance during solid-phase synthesis. For most purposes the mechanically stable beaded gel resins are preferred. These resins are homogeneous, and the loading and physical and chemical properties can easily be varied. Optimal properties have been obtained by radical polymerization of end group acryloylated long-chain polyethylene glycols. However, polystyrene resins or amide bond free PEG-based resins may be more suited for general organic synthesis where reactivity of radicals, carbenes, carbanions, carbenium ions, or strong Lewis acids have to be considered. Loading of the resins can have a dramatic effect on the outcome of a synthesis and has to be considered separately for each synthesis. Synthesis of long peptides with 50-100 amino acids imposes completely different requirements on the performance, swelling, and loading than a large-scale synthesis of, for example, the pentapeptide enkephalin. Automated multiple synthesizers constructed for columns of beaded gel or composite supports are available from many suppliers. It is therefore expected that the optimization of support properties will continue in order to meet new synthetic challenges. In the synthesis for solid-phase screening of binding of biomolecules to ligands directly on the resin beads, it is an advantage if the resin is not permeable to the biomolecule so unbound molecules can easily be removed by washing. This is the case with polystyrene-based resins, but they do, however, often show nonspecific adhesion of proteins owing to the hydrophobic character of the polystyrene. Modification of the functional groups of polystyrene with polyethylene glycol as spacers for synthesis of the binding ligands can increase the available ligand concentration on the bead surface and eliminate most of the nonspecific adhesion. In contrast to binding studies, solid-phase assays of enzymes require beads that are permeable to the enzyme, as the progress of reaction can be followed and the product of reaction analyzed. The available amount on the surface of the polystyrene-based beads (approximately 0.3%) is not enough for product analysis. Therefore, in the case of enzyme assays, highly swelling permeable PEG-based gel resins or functionalized surfaces of a polar and porous matrix are preferred.
Meldal
M
M
Carlsberg Laboratory, Department of Chemistry, Valby, Denmark.
D002621:Chemistry / Q000379:methods*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D012116:Resins, Plant / Q000737:chemistry*
D010455:Peptides; D012116:Resins, Plant