A peptide is composed of a short sequence of amino acids connected by peptide bonds.
Peptide synthesis is an active field in protein and peptide chemistry, which typically involves the sequential addition of amino acids in a defined order to form the peptide chain by chemical methods. The main synthesis methods are liquid-phase and solid-phase synthesis. Compared to LPPS, SPPS has the advantages of being faster, simpler, with fewer side reactions, and higher yields.
Standard SPPS method, including Boc (benzyl )and Fmoc (tBu ) strategies .
Boc (benzyl ) strategy
In this synthesis approach, Chloromethylated, hydroxymethylated polystyrene and p-methoxybenzyl (PMA) resins are used as solid supports. The α-amino group is protected with t-butoxycarbonyl (Boc), while side chain groups of amino acids are protected with benzyl derivatives. The Boc group is removed using neat TFA or TFA in CH2Cl2, and at the end of the synthesis, side-chain protecting groups and peptide-resin linkages are removed with a strong acid like anhydrous hydrofluoric acid (HF)or TFMSA.
Fmoc (tBu ) strategy
In this synthesis approach, Wang-resin, 2-Chlorotrityl Chloride Resin, Rink amide-AM Resin, Rink amide-MBHA resins are used as solid supports.The α-amino group is protected with 9-fluorenylmethoxycarbonyl (Fmoc), while side chain groups of amino acids are protected with acid-labile protecting groups. The Fmoc group is removed using 20% piperidine in DMF, and at the end of the synthesis, side-chain protecting groups and peptide-resin linkages are removed with 1%-95% TFA. Fmoc SPPS is currently the preferred method for peptide synthesis.