Abstract The custom peptide synthesis, photolytic detachment from the solid support and purification in solution, of a fully-protected octapeptide containing a methionine residue (protected as the sulphoxide) is described. Protection of methionine in this manner avoids problems associated with the oxidation of this residue during the photolysis. The peptide has been purified by medium pressure liquid chromatography using solvent mixtures containing a high proportion of dimethylformamide in order to avoid precipitation of the peptide on the column.
Convergent solid-phase custom peptide synthesis involving the coupling of protected peptide segments on a solid support performed in a β-sheet disrupting solvent consisting of a mixture of CHCl3 and phenol (v/v, 3/1), proceeded smoothly without danger of epimerization or of significant phenyl ester formation with the carboxyl component when diisopropylcarbodiimide (DIC) was used in the presence of 1-hydroxy-7-azabenzotriazole (HOAt) or 6-chloro-1-hydroxybenzotriazole (Cl-HOBt).
In particular, this synthetic strategy using the CHCl3 and phenol mixed solvent proved to be essential for coupling sparingly soluble segments even with difficult sequences. The present approach was successfully applied to the synthesis of amyloid β-peptide (Aβ) (1-40) and also its reversed Aβ (40-1) as an inactive control peptide.