Harrison Katriona, Mackay Angus S, Kambanis Lucas, Maxwell Joshua W C, Payne Richard J
School of Chemistry, The University of Sydney, Sydney, New South Wales, Australia.
Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Sydney, Sydney, New South Wales, Australia.
Nat Rev Chem. 2023 Jun;7(6):383-404. doi: 10.1038/s41570-023-00493-y. Epub 2023 May 12.
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.
自然界中生物分子的同手性，如DNA、RNA、肽和蛋白质，在地球上生命的建立和维持过程中发挥了关键作用。这种手性偏好也为合成化学家提供了机会，来生成具有相反手性的分子，从而解锁有价值的新特性和应用。化学蛋白质合成领域的进展为众多“镜像”蛋白质（即完全由D-氨基酸而非标准L-氨基酸组成的蛋白质）的产生奠定了基础，而这些蛋白质无法通过重组表达技术获得。本综述旨在突出合成镜像蛋白质的近期研究工作，重点关注用于获取这些复杂生物分子的现代合成策略，以及它们在蛋白质晶体学、药物发现和镜像生命创造中的应用。
