The homochirality of biomolecules in nature, such as DNA, RNA, peptides and proteins, has played a critical role in establishing and sustaining life on Earth. This chiral bias has also given synthetic chemists the opportunity to generate molecules with inverted chirality, unlocking valuable new properties and applications. Advances in the field of chemical protein synthesis have underpinned the generation of numerous 'mirror-image' proteins (those comprised entirely of D-amino acids instead of canonical L-amino acids), which cannot be accessed using recombinant expression technologies. This Review seeks to highlight recent work on synthetic mirror-image proteins, with a focus on modern synthetic strategies that have been leveraged to access these complex biomolecules as well as their applications in protein crystallography, drug discovery and the creation of mirror-image life.
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