Much current interest in chemical biology focuses on the transmembrane domains of proteins, which have emerged as targets for the development of novel diagnostics and therapeutics. Integral membrane proteins are a group of important biomolecules that play pivotal roles in many cellular activities. Previous studies primarily focused on the extra- and/or intracellular domains of membrane proteins. However, the importance of transmembrane regions in the regulation of protein complexes is beginning to emerge. As such, a number of methods for designing and testing novel exogenous peptides that recognize transmembrane targets and modulate cellular functions have been developed. This Review outlines current methodologies for developing these transmembrane probes that may provide useful tools to study a variety of biological phenomena in the membrane.
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