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.
| Original language | English (US) |
|---|---|
| Article number | 4304 |
| Journal | Nature communications |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2020 |
Funding
This work was supported by the Army Research Office (W911NF-16-1-0372) and the National Science Foundation (MCB-1716766). M.C.J. also acknowledges the David and Lucile Packard Foundation and the Dreyfus Teacher-Scholar program. We thank Dr. Ashty Karim for critical reading of the manuscript. This work made use of the Integrated Molecular Structure Education and Research Center at Northwestern University.
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy