Peptide Synthesis Overview

Introduction

Proteins are present in every living cell and possess a variety of biochemical activities. They appear as enzymes, hormones, antibiotics, and receptors. They compose a major portion of muscle, hair, and skin. Consequently, scientists have been very interested in synthesizing them in the laboratory. This interest has developed into a major synthetic field known as Peptide Synthesis. The major objectives in this field are four-fold:

• To verify the structure of naturally occurring peptides as determined by degradation techniques.

• To study the relationship between structure and activity of biologically active protein and peptides and establish their molecular mechanisms.

• To synthesize peptides that are of medical importance such as hormones and vaccines.
  

• To develop new peptide-based immunogens.

Solid-Phase Peptide Synthesis (SPPS)

SPPS is the industry norm for small and meso-scale production of peptides. In SPPS, the first amino acid and nascent peptide is C-terminally linked to a solid-phase resin; typically, polystyrene or polyacrylamide. This process of physically linking the peptide to solid-phase support gives rise to SPPS’s primary advantage: the capacity to limit side-reactions by washing reactants and waste products during every step of extension.

The solid support is a synthetic polymer that bears reactive groups such as -OH. These groups are made so that they can react easily with the carboxyl group of an N-a-protected amino acid, thereby covalently binding it to the polymer. The amino protecting group (X) can then be removed and a second N-a-protected amino acid can be coupled to the attached amino acid. These steps are repeated until the desired sequence is obtained. At the end of the synthesis, a different reagent is applied to cleave the bond between the C-terminal amino acid and the polymer support; the peptide then goes into solution and can be obtained from the solution.