Affordable Access

deepdyve-link
Publisher Website

Maximizing Output in RNA-Programmed Peptidyl-Transfer Reactions.

Authors
  • Di Pisa, Margherita1
  • Hauser, Anett1
  • Seitz, Oliver1
  • 1 Department of Chemistry, Humboldt Universität zu Berlin, Brook Taylor Strasse 2, 12849, Berlin, Germany. , (Germany)
Type
Published Article
Journal
ChemBioChem
Publisher
Wiley (John Wiley & Sons)
Publication Date
May 04, 2017
Volume
18
Issue
9
Pages
872–879
Identifiers
DOI: 10.1002/cbic.201600687
PMID: 28106939
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

A chemical reaction that is triggered by a specific RNA molecule might provide opportunities for the design of artificial feedback loops. We envision a peptidyl transfer reaction in which mRNA encoding an antiapoptotic protein would instruct the synthesis of apoptosis-inducing peptides. In this study, we used the RNA-programmed synthesis of a 16-mer peptide derived from the BH3 domain of the protein Bak, which inhibits the antiapoptotic protein Bcl-xL . The reaction involves the transfer of a thioester-linked donor peptide fragment from one PNA conjugate to an acceptor peptide-PNA conjugate. We asked two key questions. What are the chemical requirements that allow RNA-templated synthesis of a 16-mer peptide to proceed at lower (nanomolar) concentrations of RNA, that is, the concentration range found in cancer cells? Will such reactions provide sufficient amounts of peptide product and sufficient affinity to interfere with the targeted protein-protein interaction? Perhaps surprisingly, the lengths of the peptides involved in peptidyl transfer chemistry have little effect on the achievable rate enhancements. However, the nature of the thioester C terminus, the distance between the targeted template annealing sites, and template affinity play important roles. The investigation revealed guidelines for the reaction design for peptidyl transfer with low amounts (1-10 nm) of RNA, yet still provide sufficient product to antagonize a protein-protein interaction. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Report this publication

Statistics

Seen <100 times