Over the past decade there has been a renaissance in the use of large polypeptides and proteins as therapeutic agents. This has led to significant demand for technologies to rapidly and efficiently access these biomolecules, especially those bearing tailor-made modifications to maximize specificity and activity or to probe biological function (e.g. through incorporation of post-translational modifications, fluorophores and/or imaging reagents).1 We have recently developed a number of synthetic, semi-synthetic and biosynthetic technologies that enable efficient production of peptides and proteins with homogeneous post-translational modifications at pre-determined sites.2,3 This talk will highlight the utility of these technologies for: (1) manufacturing peptidic drugs under continuous flow conditions,4 (2) generating proteins with site-specific and homogeneous post-translational modifications,5,6 (3) creating lipidated synthetic vaccines,7 and (4) rapid production of libraries of modified proteins for performing “medicinal chemistry on proteins.”8
References
1. S. Kulkarni et al. Nature Rev. Chem. 2018, 2, 0122.
2. N. Mitchell et al. J. Am. Chem. Soc.2015, 137, 14011.
3. T. Chisholm et al. J. Am. Chem. Soc.2020, 142, 1090-1100
4. B. Premdjee et al. J. Am. Chem. Soc.2021, 143, 5336.
5. C. Hanna et al. Proc. Natl. Acad. Sci. U. S. A. 2021, e2013730118.
6. L. Dowman et al. Nature Commun. 2022, in press
7. E. Watson et al. Proc. Natl. Acad. Sci. U. S. A. 2019, 116, 13873.