Ribosome-mediated polymerization of long chain carbon and cyclic amino acids into peptides in vitro

Joongoo Lee, Kevin J. Schwarz, Do Soon Kim, Jeffrey S. Moore () and Michael C. Jewett ()
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Joongoo Lee: Northwestern University
Kevin J. Schwarz: University of Illinois at Urbana-Champaign
Do Soon Kim: Northwestern University
Jeffrey S. Moore: University of Illinois at Urbana-Champaign
Michael C. Jewett: Northwestern University

Nature Communications, 2020, vol. 11, issue 1, 1-8

Abstract: Abstract Ribosome-mediated polymerization of backbone-extended monomers into polypeptides is challenging due to their poor compatibility with the translation apparatus, which evolved to use α-L-amino acids. Moreover, mechanisms to acylate (or charge) these monomers to transfer RNAs (tRNAs) to make aminoacyl-tRNA substrates is a bottleneck. Here, we rationally design non-canonical amino acid analogs with extended carbon chains (γ-, δ-, ε-, and ζ-) or cyclic structures (cyclobutane, cyclopentane, and cyclohexane) to improve tRNA charging. We then demonstrate site-specific incorporation of these non-canonical, backbone-extended monomers at the N- and C- terminus of peptides using wild-type and engineered ribosomes. This work expands the scope of ribosome-mediated polymerization, setting the stage for new medicines and materials.

Date: 2020
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DOI: 10.1038/s41467-020-18001-x

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