Synthesis and applications of mirror-image proteins

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 prop...

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Published inNature reviews. Chemistry Vol. 7; no. 6; pp. 383 - 404
Main Authors Harrison, Katriona, Mackay, Angus S, Kambanis, Lucas, Maxwell, Joshua W C, Payne, Richard J
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.06.2023
Subjects
Amino acids
Amino Acids - chemistry
Biomolecules
Chemical synthesis
Chirality
Crystallography
Peptides
Protein synthesis
Proteins
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Summary: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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ISSN:2397-3358
2397-3358
DOI:10.1038/s41570-023-00493-y