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The á-helix is the most abundant secondary structural element in proteins and is an important structural domain for mediating protein-protein and protein-nucleic acid interactions. Strategies for the rational design and synthesis of á-helix mimetics have not matured as well as other secondary structure mimetics such as strands and turns. This perspective will focus on developments in the design, synthesis and applications of á-helices and mimetics, particularly in the last 5 years. Examples where synthetic compounds have delivered promising biological results will be highlighted as well as opportunities for the design of mimetics of the type I á-helical antifreeze proteins. © The Royal Society of Chemistry.