Design of transmembrane peptides: coping with sticky situations.

Membrane proteins have central roles in cellular processes ranging from nutrient uptake to cell-cell communication, and are key drug targets. However, research on α-helical integral membrane proteins is in its relative infancy vs. water-soluble proteins, largely because of their water insolubility when extracted from their native membrane environment. Peptides with sequences that correspond to the membrane-spanning segments of α-helical integral membrane proteins, termed transmembrane (TM) peptides, provide valuable tools for the characterization of these molecules. Here we describe in detail protocols for the design of TM peptides from the sequences of natural α-helical integral membrane proteins and outline strategies for their synthesis and for improving their solubility properties.