Notwithstanding great advances in the engineering and structural analy
sis of globular proteins, relatively limited success has been achieved
with membrane proteins-due largely to their intrinsic high insolubili
ty and the concomitant difficulty in obtaining crystals. Pi-ogress wit
h de novo synthesis of model membrane-interactive peptides presents an
opportunity to construct simpler peptides with definable structures,
and permits one to approach an understanding of the properties of the
membrane proteins themselves. In the present article, we review how ou
r laboratory and others have used peptide approaches to assess the det
ailed intel actions of peptides with membranes, and primary folding at
membrane surfaces and in membranes. Structural studies of model pepti
des identified the existence of a ''threshold hydrophobicity,'' which
controls spontaneous peptide insertion into membranes. Related studies
of the relative helicity of peptides in organic media such as n-butan
ol indicate that the helical propensity of individual residues-not sim
ply their hydrophobicity-may dictate the conformations of peptides in
membranes. The over-all experimental results provide fundamental guide
lines for membrane protein engineering. (C) 1998 John Wiley & Sons, In
c.