Abstract
An 82-residue-long chimeric peptide was synthesised by solid phase peptide synthesis (SPPS), following the Fmoc protocol. Microwave (MW) radiation-assisted synthesis was compared to standard synthesis using low loading (0.20 mmol/g) of polyethylene glycol (PEG) resin. Similar synthetic difficulties were found when the chimeric peptide was obtained via these two reaction conditions, indicating that such difficulties were inherent to the sequence and could not be resolved using MW; by contrast, the number of coupling cycles and total reaction time became reduced whilst crude yield and percentage recovery after purification were higher for MW radiation-assisted synthesis.
Highlights
Bruce Merrifield developed solid phase peptide synthesis (SPPS) in 1963; this involves a solid support where the peptide becomes elongated and excess reagents and by-products being withdrawn through simple filtration after every reaction step [1,2].Significant advances have been made in SPPS; this methodology has involved difficulties regarding synthesis in some cases, these being very important concerning difficult peptide sequences having severe inefficiencies regarding acylation and deprotection reactions depending on peptide sequence of amino acid residues
Loading resin was initially reduced from 0.60 mmol/g to 0.20 mmol/g to minimise the probability of synthesis difficulties caused by aggregation between adjacent chains (β-sheet secondary structure) during peptide elongation over the solid support
A single signal for the 11th residue was observed in the chromatogram during the first standard synthesis control; this was observed in the MW-assisted strategy (Table 1, Figure S1)
Summary
Bruce Merrifield developed solid phase peptide synthesis (SPPS) in 1963; this involves a solid support where the peptide becomes elongated and excess reagents and by-products being withdrawn through simple filtration after every reaction step (incorporating α-amino and deprotection) [1,2].Significant advances have been made in SPPS; this methodology has involved difficulties regarding synthesis in some cases, these being very important concerning difficult peptide sequences having severe inefficiencies regarding acylation and deprotection reactions depending on peptide sequence of amino acid (aa) residues. Peptide sequences containing much hydrophobic aa, bulky side chains or bulky protecting groups are more prone to such inefficiencies, thereby producing peptide chain deletion or truncation, in turn, is the product of peptide-resin and/or secondary structure (mostly β-sheet) aggregation causing steric hindrance [3]. These associations produce low peptide-resin complex solvation and low reagent accessibility to reaction sites. Such complications could be significant regarding long peptide synthesis because there is the high likelihood of interactions between adjacent chains and steric hindrance; long peptides require more reaction steps regarding coupling and deprotection reactions, thereby increasing the probability of incomplete reactions [4,5,6].
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