The world in which we live is homochiral. The ribose units that form the backbone of DNA and RNA are all D-configured and the encoded amino acids that comprise the proteins of all living species feature an all-L-configuration at the α-carbon atoms. The homochirality of α-amino acids is essential for folding of the peptides into well-defined and functional 3D structures and the homochirality of D-ribose is crucial for helix formation and base-pairing. The question of why nature uses only encoded L-α-amino acids is not understood. Herein, we show that an RNA-peptide world, in which peptides grow on RNAs constructed from D-ribose, leads to the self-selection of homo-L-peptides, which provides a possible explanation for the homo-D-ribose and homo-L-amino acid combination seen in nature.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/anie.202319235 | DOI Listing |
Angew Chem Int Ed Engl
May 2024
Department of Chemistry, Institute for Chemical Epigenetics (ICE-M), Ludwig-Maximilians-Universität (LMU) München, Butenandtstrasse 5-13, 81377, Munich, Germany.
The world in which we live is homochiral. The ribose units that form the backbone of DNA and RNA are all D-configured and the encoded amino acids that comprise the proteins of all living species feature an all-L-configuration at the α-carbon atoms. The homochirality of α-amino acids is essential for folding of the peptides into well-defined and functional 3D structures and the homochirality of D-ribose is crucial for helix formation and base-pairing.
View Article and Find Full Text PDFJ Pept Sci
July 2023
Department of Chemistry, Humboldt University Berlin, Berlin, Germany.
Nucleic acid-templated chemistry opens the intriguing prospect of triggering the synthesis of drugs only in diseased cells. Herein, we explore the feasibility of using RNA-templated chemical reactions for the activation of a known Smac peptidomimetic compound (SMC), which has proapoptotic activity. Two peptide nucleic acid (PNA) conjugates were used to enable conditional activation of a masked SMC by reduction of an azide either by Staudinger reduction or catalytic photoreduction using a ruthenium complex.
View Article and Find Full Text PDFFront Mol Biosci
November 2022
Department of Chemistry, Emory University, Atlanta, GA, United States.
The Central Dogma highlights the mutualistic functions of protein and nucleic acid biopolymers, and this synergy appears prominently in the membraneless organelles widely distributed throughout prokaryotic and eukaryotic organisms alike. Ribonucleoprotein granules (RNPs), which are complex coacervates of RNA with proteins, are a prime example of these membranelles organelles and underly multiple essential cellular functions. Inspired by the highly dynamic character of these organelles and the recent studies that ATP both inhibits and templates phase separation of the fused in sarcoma (FUS) protein implicated in several neurodegenerative diseases, we explored the RNA templated ordering of a single motif of the Aβ peptide of Alzheimer's disease.
View Article and Find Full Text PDFBioorg Med Chem
July 2022
Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, D-12489 Berlin, Germany. Electronic address:
Nucleic acid-programmed reactions find application in drug screening and nucleic acid diagnosis, and offer prospects for a RNA-sensitive prodrug approach. We aim for the development of a nucleic acid-templated reaction providing nucleic acid-linked molecules that can act on intracellular protein targets. Such reactions would be useful for in situ drug synthesis and activity-based DNA-encoded library screening.
View Article and Find Full Text PDFCommun Chem
October 2021
Organic and Biomimetic Chemistry Research Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000, Ghent, Belgium.
Ligation methodologies featuring bio-orthogonal units and leading to the formation of a stable adduct are the ideal candidates for being applied in a biological context. However, most of the available strategies rely on highly reactive species that require careful handling, or on the activation of pro-reactive functional groups. We here report on a proximity-induced ligation reaction that relies on a stable 2,5-dione, that can be conveniently generated under acidic conditions from a 2,5-dialkylfuran building block, and hydrazine nucleophiles.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!