Ribosomal Formation of Thioamide Bonds in Polypeptide Synthesis
It has been well established that the ribosome can accept various nucleophiles on the Xacyl-tRNA in the A site during elongation, where X can be amino, N-alkyl-amino, hydroxy, and thiol groups. However, it remains elusive that the ribosome is able to accept an electrophile in the P site other than t...
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| Published in: | Journal of the American Chemical Society Vol. 141; no. 51; pp. 20004 - 20008 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
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26-12-2019
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| Abstract | It has been well established that the ribosome can accept various nucleophiles on the Xacyl-tRNA in the A site during elongation, where X can be amino, N-alkyl-amino, hydroxy, and thiol groups. However, it remains elusive that the ribosome is able to accept an electrophile in the P site other than the carboxyl group during elongation. Here we report ribosomal formation of a thioamide bond in the mRNA-dependent polypeptide synthesis. In this study, amino(carbothio)acyl-tRNA was prepared by flexizyme and used for the expression of peptides containing a thioamide bond in the nascent peptide chain. We give strong evidence that the thioamide-peptide was formed but accompanied by the amide counterpart due to rapid carbo(S-to-O) exchange during the preparation of amino(carbothio)acyl-tRNA. We also demonstrate the ribosomal formation of thioamide and N-methyl-thioamide bonds in linear as well as macrocyclic peptide scaffolds in the mRNA-dependent manner, showing its potential for applications in peptide-based drug discovery and studying peptide/protein structure and function. |
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| AbstractList | It has been well established that the ribosome can accept various nucleophiles on the Xacyl-tRNA in the A site during elongation, where X can be amino,
-alkyl-amino, hydroxy, and thiol groups. However, it remains elusive that the ribosome is able to accept an electrophile in the P site other than the carboxyl group during elongation. Here we report ribosomal formation of a thioamide bond in the mRNA-dependent polypeptide synthesis. In this study, amino(carbothio)acyl-tRNA was prepared by flexizyme and used for the expression of peptides containing a thioamide bond in the nascent peptide chain. We give strong evidence that the thioamide-peptide was formed but accompanied by the amide counterpart due to rapid carbo(S-to-O) exchange during the preparation of amino(carbothio)acyl-tRNA. We also demonstrate the ribosomal formation of thioamide and
-methyl-thioamide bonds in linear as well as macrocyclic peptide scaffolds in the mRNA-dependent manner, showing its potential for applications in peptide-based drug discovery and studying peptide/protein structure and function. It has been well established that the ribosome can accept various nucleophiles on the Xacyl-tRNA in the A site during elongation, where X can be amino, N-alkyl-amino, hydroxy, and thiol groups. However, it remains elusive that the ribosome is able to accept an electrophile in the P site other than the carboxyl group during elongation. Here we report ribosomal formation of a thioamide bond in the mRNA-dependent polypeptide synthesis. In this study, amino(carbothio)acyl-tRNA was prepared by flexizyme and used for the expression of peptides containing a thioamide bond in the nascent peptide chain. We give strong evidence that the thioamide-peptide was formed but accompanied by the amide counterpart due to rapid carbo(S-to-O) exchange during the preparation of amino(carbothio)acyl-tRNA. We also demonstrate the ribosomal formation of thioamide and N-methyl-thioamide bonds in linear as well as macrocyclic peptide scaffolds in the mRNA-dependent manner, showing its potential for applications in peptide-based drug discovery and studying peptide/protein structure and function. |
| Author | Maini, Rumit Goto, Yuki Katoh, Takayuki Suga, Hiroaki Kimura, Hiroyuki Takatsuji, Ryo |
| AuthorAffiliation | JST-CREST Department of Chemistry, Graduate School of Science The University of Tokyo |
| AuthorAffiliation_xml | – name: – name: The University of Tokyo – name: Department of Chemistry, Graduate School of Science – name: JST-CREST |
| Author_xml | – sequence: 1 givenname: Rumit surname: Maini fullname: Maini, Rumit – sequence: 2 givenname: Hiroyuki orcidid: 0000-0002-5297-3264 surname: Kimura fullname: Kimura, Hiroyuki – sequence: 3 givenname: Ryo surname: Takatsuji fullname: Takatsuji, Ryo – sequence: 4 givenname: Takayuki surname: Katoh fullname: Katoh, Takayuki – sequence: 5 givenname: Yuki orcidid: 0000-0003-4317-0790 surname: Goto fullname: Goto, Yuki – sequence: 6 givenname: Hiroaki orcidid: 0000-0002-5298-9186 surname: Suga fullname: Suga, Hiroaki email: hsuga@chem.s.u-tokyo.ac.jp |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31815469$$D View this record in MEDLINE/PubMed |
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| Title | Ribosomal Formation of Thioamide Bonds in Polypeptide Synthesis |
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