Peptides are small polymers of amino-acids, which can be used in a wide variety of experiments. They can be used as protein mimics and antigens, or as monoclonal or polyclonal antibodies. In addition, they can be used as a means of treatment for viral and bacterial infections.
One of the first synthesized peptide drugs was enfuvirtide. This peptide was based on the tryptic peptides of S. pyogenes Cas9. The sequences of these tryptic peptides were used as the starting material for a library of crosslinked peptides.
Chemical synthesis is a fast and inexpensive way to produce peptides. However, it can be limited by the number of amino acids that can be incorporated. It also may not be suitable for synthesis of larger bioactive proteins.
Crosslinked peptides can be obtained by using a chemoselective ligation reaction. A trypsin-like reagent reacts with the amino-acid residue of the N-terminus of the peptide. When the amine of one amino acid reacts with the carboxylic acid group of the other, the peptide is crosslinked.
Another method is called click reaction. Two short synthetic peptides are incorporated in a solution. These peptides are then purified and confirmed by MALDI-MS.
Solid phase peptide synthesis (SPPS) is a process for constructing a peptide chain in successive reactions of amino acid derivatives. Initially, the peptide is synthesized as an exact copy of a protein fragment. Subsequent peptides are reacted on a macroscopically insoluble resin support.
The main advantages of SPPS over solution peptide synthesis are the use of a solid support, which avoids the need for downstream purification, and the ease with which the product peptide can be separated from the reagents. Additionally, a solid support makes it easier to identify and remove the reagents and residues that are not essential for the peptide’s function.