Chemical synthesis of highly hydrophobic peptides and proteins remains a ch
allenging problem. Strong interchain associations within the peptide-resin
matrix have to be overcome. A synthetic strategy for solid phase peptide sy
nthesis is proposed, mainly based on prolonged coupling time using aprotic
polar solvent mixtures. A tailored chromatographic purification was require
d to obtain a sample sufficiently pure for structural analysis. In this wor
k, the total chemical synthesis of the membrane-embedded yeast mitochondria
l ATP synthase subunit 8 is described. The quality of the synthetic protein
was checked by electrospray mass spectrometry, its tendency to adopt alpha
-helical secondary structure is evidenced by circular dichroism spectroscop
y. Copyright (C) 1999 European Peptide Society and John Wiley & Sons, Ltd.