Efficient manual Fmoc solid-phase synthesis of the N-terminal segment of surfactant protein B (SP-B(1-25))

The N-terminal 25 residue segment of human surfactant protein B (SP-B(1-25)) was synthesised in 26% yield by manual Fmoc solid-phase peptide synthesis (Fmoc SPPS) using low-loading Fmoc-Gly-Wang resin. Substantial oxidation of Met(21) occurred during the synthesis, and the addition of Bu(4)NBr to a TFA/water/EDT/TIS cleavage cocktail enabled facile reduction of Met(O)(21)-SP-B(1-25) to SP-B(1-25). The methods described herein are generally applicable to the Fmoc SPPS of difficult sequences containing methionine.