Peptide Synthesis - Solid Supports

Solid Supports

The name solid support implies that reactions are carried out on the surface of the support, but this is not the case. Reactions also occur within these particles, and thus the term "solid support" better describes the insolubility of the polymer. The physical properties of the solid support, and the applications to which it can be utilized, vary with the material from which the support is constructed, the amount of cross-linking, as well as the linker and handle being used. Most scientists in the field believe that supports should have the minimum amount of cross-linking to confer stability. This should result in a well-solvated system where solid-phase peptide synthesis can be carried out. Nonetheless, the characteristics of an efficient solid support include:

1. It must be physically stable and permit the rapid filtration of liquids, such as excess reagents
2. It must be inert to all reagents and solvents used during SPPS
3. It must swell extensively in the solvents used to allow for penetration of the reagents
4. It must allow for the attachment of the first amino acid

There are four primary types of solid supports:

1. Gel-type supports: These are highly solvated polymers with an equal distribution of functional groups. This type of support is the most common, and includes:
   • Polystyrene: Styrene cross-linked with 1-2% divinylbenzene
   • Polyacrylamide: A hydrophilic alternative to polystyrene
   • Polyethylene glycol (PEG): PEG-Polystyrene (PEG-PS) is more stable than polystyrene and spaces the site of synthesis from the polymer backbone
   • PEG-based supports: Composed of a PEG-polypropylene glycol network or PEG with polyamide or polystyrene
2. Surface-type supports: Many materials have been developed for surface functionalization, including controlled pore glass, cellulose fibers, and highly cross-linked polystyrene.
3. Composites: Gel-type polymers supported by rigid matrices.