Efficient Manual Fmoc Solid-Phase Synthesis of the N-Terminal Segment of Surfactant Protein B (SP-B1-25)

The N-terminal 25 residue segment of human surfactant protein B (SP-B1-25) was synthesised in 26% yield by manual Fmoc solid-phase peptide synthesis (Fmoc SPPS) using low-loading Fmoc-Gly-Wang resin. Substantial oxidation of Met21 occurred during the synthesis, and the addition of Bu4NBr to a TFA/water/EDT/TIS cleavage cocktail enabled facile reduction of Met(O)21-SP-B1-25 to SP-B1-25. The methods described herein are generally applicable to the Fmoc SPPS of difficult sequences containing methionine.