What Is Solid Phase Peptide Synthesis (SPPS)?
SPPS has emerged as the preferred method for constructing peptides due to its efficiency, flexibility, and scalability. SPPS allows the stepwise construction of peptides, starting from the C-terminus to the N-terminus, by immobilizing the growing peptide chain on a solid support matrix. The solid support matrix is an insoluble resin, usually small polymeric resin beads. In this synthesis technology, the reactants in the liquid phase and the products fixed on the solid phase carrier can be separated by simple solid-liquid separation, thereby meeting the purification requirements and simplifying the experimental operation.
Alfa Chemistry offers a wide range of resins with different functionality, joining chemistries and loading capabilities, giving our customers the freedom to choose the resin that best suits their specific synthesis requirements.
Scheme of solid-phase peptide synthesis 
Common Peptide Synthesis Resins
At Alfa Chemistry, we have applied our decades-long expertise to develop high-quality, custom-engineered resins that facilitate SPPS. Our resins act as the stable backbone, efficiently anchoring amino acids and other reactive intermediates during the synthesis process.
Classification According to Polymer:
- Polystyrene-based resins
They provide a stable and inert support for peptide synthesis due to their high mechanical strength and good chemical stability.
- Polyacrylamide-based resins
They offer a high binding capacity, good swelling properties, and compatibility with a wide range of synthesis conditions.
- Polyethylene glycol-based resins
They are known for their high swelling properties, which allow efficient attachment of amino acids during peptide synthesis.
Classification According to Functional Groups:
- Rink Amide Resins
Rink amide resins contain a linker that enables the attachment of peptides through an amide bond. They are often used for the synthesis of peptides with C-terminal carboxylic acids.
- Wang Resins
This resin is functionalized with a p-methylbenzhydrylamine group, which acts as the anchor for peptide synthesis. This functional group allows for easy attachment and detachment of amino acids through the use of acid and base treatment.
- 2-Chlorotrityl Resins
This resin possesses a 2-chlorotrityl chloride functional group, which acts as an anchor for peptide synthesis.
Boc and Fmoc Solid Phase Synthesis Strategies
Tert-butoxycarbonyl (Boc) method
In the early days, peptide synthesis relied on Boc as a temporary N-terminal α-amino protecting group. During the synthesis, trifluoroacetic acid (TFA) was used to remove the protecting group and then perform condensation. However, the use of hydrofluoric acid (dangerous solvent) in the resin cleavage process of peptides limits the application of the Boc method to a certain extent.
9-Fluorenylmethoxycarbonyl (Fmoc) method
The strategy of using N-terminal Fmoc protection corresponds to a gentler solid-phase synthesis method of peptides. During the synthesis of the peptide chain, piperidine solution was used to remove the Fmoc protecting group, and finally TFA was used to remove the polypeptide side chain protecting group and connecting arm. The good safety of Fmoc solid-phase synthesis method and its compatibility with acid-sensitive modification groups (such as phosphorylation modification, glycosylation modification, etc.) make it have a wider range of applications.
- Jose M. Palomo. RSC Adv., 2014,4, 32658-32672.2