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

Authors:
; ; ; ;
Award ID(s):
1716766
Publication Date:
NSF-PAR ID:
10187109
Journal Name:
Nature Communications
Volume:
11
Issue:
1
ISSN:
2041-1723
Publisher:
Nature Publishing Group
Sponsoring Org:
National Science Foundation
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