5 Advantages of Solid Phase Peptide Synthesis

More people have been exploring the utility of peptides in recent years due to the wide variety of applications. The peptide synthesis process involves linking amino acids via peptide bonds. Solid phase synthesis is a commonly used approach in peptide synthesis, given the ease with which peptide linear’s precursors are produced. The peptides important to academia and industry are primarily synthesized in the solid phase. This method has many advantages over liquid-phase peptide synthesis for the preparation and large-scale manufacturing of synthetic peptides. 

The concept of solid phase peptide synthesis is to retain the chemistry that has been proven in the solution while adding a covalent attachment step. The solid phase peptide synthesis method has several advantages in building complex peptide-based macrocycles. This article looks at some of the main benefits of using this method in peptide synthesis.

1. It makes it easy to modify amino acids within the peptide region. 

The solid phase peptide synthesis involves adding protected amino acid derivatives to a growing peptide chain immobilized in a solid phase. This method makes modifying the amino acids within a peptide region easy. It can also help simplify analog synthesis, providing opportunities to synthesize peptides. The improved safety profile of solid phase peptide synthesis has allowed inexperienced chemists to undertake the peptide synthesis efforts easily. 

The process starts with immobilizing an appropriately protected amino acid to a linker-bound polystyrene-based resin. The peptide elongation is achieved by the deprotection of the leading chain group followed by the coupling of the next appropriately protected amino acids. This deprotection is essential to secure high-quality products during protein synthesis.

2. Easy purification

It’s possible to purify peptides with different physicochemical properties. The minimum requirement of peptide purity depends on your application and essay. However, since the most recommended purity is over 90%, you need a scheme that can make it easy to purify the peptides in large quantities. Solid phase peptide synthesis has more advantages over solution phase protein services when you want to purify large amounts of peptides.

You can quickly purify the peptides by preparative or semi-preparative HPLC. This purification is quick as it considers factors like the gradient and flow rate as well as the sequence of the peptide. Compared to the liquid phase peptide synthesis scheme, the solid phase peptide synthesis uses reverse phase chromatography that removes all impurities. 

3. Rapid generation of linear peptide intermediate

The solid phase method is superior when comparing the solution phase to a solid phase route in peptide synthesis. The solution phase approach is tedious and involves the cyclization of a ridged heterocyclic precursor, while the SPPS involves the rapid generation of a flexible linear peptide. The definition of a linear precursor involves a modified reaction that starts with an alanine residue attached to a resin. Sequential coupling of residues and cleavage generates a peptide precursor. 

One of the critical requirements of regenerative biomaterials is that they support the in-growth and proliferation of endogenous cells. Solid phase peptide synthesis is the best approach to achieving rapid tissue regeneration. It helps synthesize peptides rapidly using common reagents to achieve synthetic peptide coupling.

Solid phase peptide synthesis offers significant advantages over synthesis in solution. A high-efficiency solid phase peptide synthesis allows multiple antigenic properties.  The use of self-assembling peptide amphiphiles is cautious in applying the regeneration of the 

4. Precedent in the synthesis of large peptides 

We can synthesize peptides using a solid phase to form a large macrocycle. This peptide synthesis is the best alternative to using the liquid phase when synthesizing peptides in high amounts. It offers a simple option for substituting serines for cysteines. The approach applies in different processes that allow for the high throughput production of peptides. Technological advancement makes it possible to mass-produce peptides in the laboratory using this method.

It’s the best method to reduce the adverse effects on peptide synthesis and facilitate large-scale peptide synthesis. Usually, incomplete deprotection results in truncated or deletion sequences that impact the process. Solid phase peptide synthesis allows you to minimize side reactions during the synthesis process by analyzing how an amino acid reactive group can bind to a functional group. This deprotection happens shortly after coupling, and once amino acids bind to the growing peptide chain.

5. It enables an efficient synthesis of customized peptides with resistance to degradation.

The solid phase peptide synthesis involves adding protected amino acid derivatives to the growing peptide chain immobilized in a solid phase. This scheme is popular because of its improved chemical stability and enhanced resistance to in situ enzymes. It makes it easy to synthesize customized peptides while resisting degradation efficiently.

It has also revolutionized synthetic accessibility to the chemist. The strategy allows creativity and imagination to prevent undesirable side effects during peptide synthesis. It also makes it easy to perform convergent synthesis that involves analyzing peptides into sequences and linking them to larger molecules. During the process, the first amino acid has the c-terminus coupled to a rigid activated support, creating a two-fold method that makes it easy to separate the peptide product from the various reactions. 

Bottom line

Researchers have widely used peptide synthesis in research studies. The solid phase peptide synthesis protocol is based on the widely used FMOC strategy that activates carboxyl groups. Compared to a solution phase, the SPPS is superior in several ways. Its ability to synthesize peptides to high purity and on a large scale has revolutionized research and allowed the development of a broader range of therapeutic agents. However, the solid phase peptide synthesis is relatively labor-intensive. There are some additional steps required in the manufacturing process.