Ribosomal Incorporation of Aromatic Oligoamides as Peptide Sidechain Appendages

Tsiamantas, Christos; Kwon, Sunbum; Rogers, Joseph M.; Douat, Céline; Huc, Ivan; Suga, Hiroaki

doi:10.1002/ange.201914654

Cited by 7 publications

(5 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…36,37 We also demonstrated elongation of amino acids bearing such aromatic oligoamides at their side chains. 38 Ad et al also reported ribosomal incorporation of Abz derivatives at the Nterminus. However, those molecules were not introduced in the main chain in the middle of peptide sequences, i.e., not by the elongation process.…”

mentioning

confidence: 95%

Ribosomal Elongation of Aminobenzoic Acid Derivatives

Katoh

Suga

2020

J. Am. Chem. Soc.

Self Cite

View full text Add to dashboard Cite

2-Aminobenzoic acid and heterocyclic amino acids are aromatic homologues of β-amino acids, but their chemical properties are quite distinct. Because of the poor nucleophilicity of the amino group conjugated with the aromatic ring, no literature reports of their successful ribosomal elongation in nascent peptide chains have appeared to date. Here we report for the first time their incorporation in nascent peptide chains by means of a reconstituted translation system in which a designer tRNAPro1E2 capable of recruiting the elongation factors EF-Tu and EF-P was charged with their derivatives and the corresponding peptides were successfully expressed. We also demonstrate the expression of macrocyclic peptides containing exotic amino acids, including aminobenzoic acid derivatives.

show abstract

mentioning

confidence: 95%

Ribosomal Elongation of Aminobenzoic Acid Derivatives

Katoh

Suga

2020

J. Am. Chem. Soc.

Self Cite

View full text Add to dashboard Cite

show abstract

“…incorporate hundreds of distinct non-canonical amino acids (ncAAs) into peptides and proteins to expand the range of genetically encoded chemistry [6][7][8][9][10] . These ncAAs have included α-, β-, γ-, δ-, ε-, ζ-, cyclic, D-, and N-alkylated amino acids [11][12][13][14][15][16][17][18][19] , as well as alternative monomers (e.g., non-amino carboxylic acids, hydroxy acids, aminoxy acids, hydrazino acids, and thioacids) [20][21][22][23][24] .…”

mentioning

confidence: 99%

Ribosome-mediated biosynthesis of pyridazinone oligomers in vitro

et al. 2022

View full text Add to dashboard Cite

The ribosome is a macromolecular machine that catalyzes the sequence-defined polymerization of L-α-amino acids into polypeptides. The catalysis of peptide bond formation between amino acid substrates is based on entropy trapping, wherein the adjacency of transfer RNA (tRNA)-coupled acyl bonds in the P-site and the α-amino groups in the A-site aligns the substrates for coupling. The plasticity of this catalytic mechanism has been observed in both remnants of the evolution of the genetic code and modern efforts to reprogram the genetic code (e.g., ribosomal incorporation of non-canonical amino acids, ribosomal ester formation). However, the limits of ribosome-mediated polymerization are underexplored. Here, rather than peptide bonds, we demonstrate ribosome-mediated polymerization of pyridazinone bonds via a cyclocondensation reaction between activated γ-keto and α-hydrazino ester monomers. In addition, we demonstrate the ribosome-catalyzed synthesis of peptide-hybrid oligomers composed of multiple sequence-defined alternating pyridazinone linkages. Our results highlight the plasticity of the ribosome’s ancient bond-formation mechanism, expand the range of non-canonical polymeric backbones that can be synthesized by the ribosome, and open the door to new applications in synthetic biology.

show abstract

“…In light of this research, tRNA Pro1E2 has recently been used as an updated GCE scaffold tRNA to improve the installation of a staggering number of translation-incompatible substrates in vitro for a number of applications (Lee et al, 2020a;Lee et al, 2020b;Lee et al, 2021b. ;Lee et al, 2022;Hammerling et al, 2020;Tsiamantas et al, 2020;Katoh and Suga, 2022b;Katoh and Suga, 2022a;Katoh and Suga, 2023b). As discussed above, this platform has been recently updated by adjusting the anticodon arm according to the anticodon sequence for further improving in vitro ncAA incorporation (Katoh and Suga, 2024), demonstrating the modular tunability of different tRNA regions.…”

Section: Improving Peptide Bond Formation and Peptidyl Transfermentioning

confidence: 99%

Tuning tRNAs for improved translation

Weiss,

Decker,

Bolano

et al. 2024

Front. Genet.

View full text Add to dashboard Cite

Transfer RNAs have been extensively explored as the molecules that translate the genetic code into proteins. At this interface of genetics and biochemistry, tRNAs direct the efficiency of every major step of translation by interacting with a multitude of binding partners. However, due to the variability of tRNA sequences and the abundance of diverse post-transcriptional modifications, a guidebook linking tRNA sequences to specific translational outcomes has yet to be elucidated. Here, we review substantial efforts that have collectively uncovered tRNA engineering principles that can be used as a guide for the tuning of translation fidelity. These principles have allowed for the development of basic research, expansion of the genetic code with non-canonical amino acids, and tRNA therapeutics.

show abstract

Ribosomal Incorporation of Aromatic Oligoamides as Peptide Sidechain Appendages

Cited by 7 publications

References 26 publications

Ribosomal Elongation of Aminobenzoic Acid Derivatives

Ribosomal Elongation of Aminobenzoic Acid Derivatives

Ribosome-mediated biosynthesis of pyridazinone oligomers in vitro

Tuning tRNAs for improved translation

Contact Info

Product

Resources

About