Peptides synthesis is performed by combining the carboxyl group of one amino acid with the amino group of another. Synthetic peptides are synthesized from the C-terminus (Carboxyl) to the N-terminus (Amine), similar to peptides in biological organisms.
Peptide synthesis is not as easy as mixing amino acids together to form amides.
If you want to form a specific sequence with many different amino acids, one must carefully control the order of the reaction and the bonds that are formed.
Peptide Synthesis: An Introduction
- e.g. mixing Glutamine E anad Serine S will yield a mixture of amides: E-S, S-E, S-S and EE and other higher order polypeptides such as E-S-S-E-E.
- Due the addition of excess amino acids to drive the reaction and
to ensure complete coupling during each synthesis step,
polymerization of amino acids into long polypeptides is common in reactions where theamino acids are not protected.
- It is therefore vital to protect and control amide bond formation between amino acids.
- Therefore, in order to control the coupling reaction and amide bond formation, protection groups are needed in peptide synthesis.
- By protecting the amide groups of one amino acid component and the carboxylic acid group of the other amino acid, specific and controlled amide bond formations can be synthesized.
- Deprotection steps are thus needed in peptide synthesis during the synthesis reaction.
- This creates a repeating synthesis flow.
- Coupling reagents can be used to activate the process of amide bond formation, making amide formation also more effective.
- Common coupling agents are: N,N'-dicyclohexylcarbodiimide (DCCI)
Did you Know?
In 1984, the Nobel Prize for chemistry was awarded to Professor Merrifield (Rockefeller University). Merrifield developed an automated version of peptide / protein synthesis which was able to produce the hormone insulin (51 amino acids).
Synthesis Flow of Peptide Synthesis
- Amino acids have protected groups added.
- Protected amino acids dissolved in a solvent such as dimethylformamide (DMF) are combined with coupling reagents are pumped through the synthesis column.
- Protective groups is removed from trailing amino acids in a deprotection reaction.
- Deprotection reagents washed away to provide clean coupling environment.
- Coupling agents such as DCCI help form amide bonds between the amid acids.
- Coupling reagents are then washed away to provide a clean deprotection environment