In organic chemistry, peptide synthesis is the creation of peptides, which are organic compounds in which multiple amino acids bind via peptide bonds.
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Peptides are synthesized by combining the carboxyl group of one amino acid with the amino group of another. While peptides created biologically are built from the C-terminus (Carboxyl) to the N-terminus (Amine), synthetic peptides are built in the reverse order.
Liquid-phase peptide synthesis is a classical approach to peptide synthesis. It has been replaced in most labs by solid-phase synthesis (see below). However, it retains usefulness in large-scale production of peptides for industrial purposes.
Solid phase peptide synthesis was pioneered by Merrifield, resulting in a paradigm shift within the peptide synthesis community. In solid-phase synthesis, small beads are treated with linkers on which peptide chains can be built. The synthesis beads will retain strong bondage to the peptides until cleaved by a reagent such as triflouroacetic Acid. The beads create a synthesis environment in which the peptide chains being created will not pass through a filter material while the reagents used to create them will.
Due to amino acid excesses used to ensure complete coupling during each synthesis step, Polymerization of amino acids is common in reactions where each amino acid is not protected. In order to prevent this polymerization, protective groups are used. This adds additional deprotection phases to the synthesis reaction, creating a repeating design flow as follows:
Currently, two protective groups are commonly used in solid-phase peptide synthesis.
The Fmoc protective group is currently a widely used protective group that will prevent polymerization and can be easily removed from the trailing end of a peptide during deprotection.
Before the Fmoc group became popular, the Boc group was a common protective group. It retains usefulness in reducing aggregation of peptides during synthesis.
Stepwise elongation, in which the amino acids are connected step-by-step in turn, is ideal for small peptides containing between 2 and 100 amino acid residues. Another method is fragment condensation, in which peptide fragments are coupled. Although the former can elongate the peptide chain without racemization, the yield drops if only it is used in the creation of long or highly polar peptides. Fragment condensation is better than stepwise elongation for synthesizing sophisticated long peptides, but its use must be restricted in order to protect against racemization.