We use a combination of chemical synthesis, electrophysiology and x-ray crystallography to study ion channels. Our research efforts are presently focused on potassium channels. We synthesize potassium channels by chemical ligation of synthetic and recombinant peptide fragments. The synthetic channels are functionally characterized using high resolution single channel measurements and structurally characterized using X-ray crystallography. Using this approach, we seek to understand the molecular mechanisms that underlie ionic selectivity and gating in K+ channels. We are also interested in extending semi-synthesis methodology to other integral membrane proteins like transporters and G protein coupled receptors. We believe that chemical access provided by semi-synthesis will open up new avenues of investigations into these systems.