Towards the total chemical synthesis of integral membrane proteins: a general method for the synthesis of hydrophobic peptide-thioester building blocks.

Modification of a peptide-(α)thioester with a sequence of six arginines on the thioester leaving group can render soluble all peptides derived from a polytopic integral membrane protein. This strategy greatly simplifies the synthesis of peptide-(α)thioester building blocks for the total chemical synthesis of integral membrane proteins by native chemical ligation.