Synthesis and biophysical characterization of highly hydrophobic transmembrane peptides

Phospholamban (PLB), a 52-membered integral membrane protein, is a major regulator of the kinetics of cardiac contractility. It is located in the sarcoplasmatic reticulum and it inhibits the activity of the resident -ATPase (SERCA2) [for recent reviews, see 1,2]. The trans-membrane domain of PLB associates to a five-stranded coiled coil which partly dissociates upon dephosphorylation of the cytoplasmatic domain. Recently, the sequence of another transmembrane peptide, located in the sarcoplasmatic reticulum, was determined and named sarcolipin (SLN) [3,4]. It shows high sequence homology with the C-terminal region of PLB, with numerous hydrophobic amino acid residues. The function of this 31-membered “proteolipid” is associated with a fast-twitch skeletal muscle ATPase (SERCA1). In an attempt to determine the biophysical properties of SLN and to compare them with PLB, we have synthesized the whole SLN peptide and the C-terminal sequence of phospholamban PLB(24-52) (Fig. 1).