3. Solid phase synthesis

The important method for the synthesis of peptides in the lab is known as solidphase peptide synthesis (SPPS) [3]. Merrifield [4] developed this method of SPPS which allows the rapid assembly of a peptide chain through successive reactions of amino acid derivatives on an insoluble porous support. Unlike ribosome protein synthesis, artificial synthesis builds peptides in the C to N direction. During solidphase peptide synthesis, each peptide is anchored to an insoluble polymer at the Cterminus.

#### 3.1 Solid support

which clearly indicates chemical synthesis of peptides is a difficult task [1]. But advances in protein synthesis today made peptide synthesis easier today which has varied applications in high-throughput biological research and drug development

Coupling of two amino acids in solution. The unprotected amine of one reacts with the unprotected carboxylic

Liquid-phase peptide synthesis is the classical method that is slow and labour intensive in which separate peptides are synthesized and then coupled together to create larger peptides. In this method chemical group is used to protect the C-

Solid-phase peptide synthesis is the most common method where the Cterminus of the first amino acid is coupled to an activated solid support, such as polystyrene or polyacrylamide. This method is advantageous as the resin acts as the

They are two methods of peptide synthesis, namely

[2] (Figure 2).

Figure 2.

66

Figure 1. Peptide structure.

Peptide Synthesis

2. Peptide synthesis

• Liquid-phase peptide synthesis

acid group of the other to form a peptide bond.

• Solid-phase peptide synthesis

terminus of the first amino acid.

Solid support in SPPS is Polystyrene, a styrene cross-linked with 1–2% divinylbenzene which is a popular carrier resin in SPPS. Other common gel-type supports include polyacrylamide and polyethylene glycol (PEG). Polystyrene is chemically inert under SPSS conditions. The solid support helps in anchoring the amino acids and formation of peptide.

#### 3.2 Protecting groups

Amino acids contain side chains with different functional groups with different reactivity. Thus different protecting groups are required. A major problem in peptide synthesis is the side reactions due to multiple reactive groups in amino acids. In order to perform peptide formation with minimal side reactions or to protect the functional groups from non-specific reactions reactive groups in the amino acids need to be blocked or protected. For this many chemical groups have been developed that bind to the amino acids and protect it. They are two types of protecting groups, namely

