Solid-Phase-Supported Chemoenzymatic Synthesis of a Light-Activatable tRNA Derivative

Anja Blümler, Harald Schwalbe, Alexander Heckel

Angew. Chem. Int. Ed.
https://doi.org/10.1002/anie.202111613

Here, we present a multi-cycle chemoenzymatic synthesis of modified RNA with simplified solid-phase handling to overcome size limitations of RNA synthesis. It combines the advantages of classical chemical solid-phase synthesis and enzymatic synthesis methods using magnetic streptavidin beads and biotinylated RNA. Successful introduction of light-controllable RNA nucleotides into the tRNAMet sequence was confirmed by gel electrophoresis and mass spectrometry. The methods tolerate modifications in the RNA phosphodiester backbone and allow introductions of photocaged and photoswitchable nucleotides as well as photocleavable strand breaks and fluorophores.

Controlling Coagulation in Blood with Red Light

Patricia Müller, Marlen Sahlbach, Simone Gasper, Prof. Dr. Günter Mayer, Priv.-Doz. Dr. Jens Müller, Prof. Dr. Bernd Pötzsch, Prof. Dr. Alexander Heckel

Angew. Chem. Int. Ed. 2021, 60, 22441.
https://doi.org/10.1002/anie.202108468 (open access)

An engineered aptamer with a Cy7-based photocleavable linker can be used as anticoagulant. With tissue-penetrating red light, the aptamer is cleaved, and blood clotting is restored in human whole blood.

Thoughts on What Chemists Can Contribute to Fighting SARS-CoV-2 - A Short Note on Hand Sanitizers, Drug Candidates and Outreach

Till Opatz, Joerg Senn-Bilfinger, Clemens Richert

Angew. Chem. 2020, 132, doi/10.1002/ange.202004721
https://onlinelibrary.wiley.com/doi/10.1002/ange.202004721
https://onlinelibrary.wiley.com/doi/10.1002/anie.202004721

A three-pronged approach for chemists to contribute to fighting the SARS-CoV-2 outbreak is proposed.

A Benzophenone‐Based Photocaging Strategy for the N7 Position of Guanosine

Lea Anhäuser, Nils Klöcker, Fabian Muttach, Florian Mäsing, Petr Špaček, Armido Studer and Andrea Rentmeister

Angewandte Chemie International Edition 2020, 59, 3161-3165.
https://doi.org/10.1002/anie.201914573 (open access)

Aryl ketones are photolabile caging groups if installed at the N7 position of guanosine or the N1 position of adenosine whereas common photocaging groups derived from the ortho‐nitrobenzyl moiety were not suitable.

Micellar Brønsted Acid Mediated Synthesis of DNA-Tagged Heterocycles

M. Klika Škopić, K. Götte, C. Gramse, M. Dieter, S. Pospich, S. Raunser, R. Weberskirch, A. Brunschweiger

https://doi.org/10.1021/jacs.9b05696

DNA-encoded libraries are increasingly used of drug identification. However, the reactivity of the DNA imposes limitations on the choice of chemical methods for encoded library synthesis. Amphiphilic block copolymers covalently functionalized with sulfonic acid moieties in the lipophilic portion assemble in water and locate the Brønsted catalyst in micelles. These acid nanoreactors enabled the reaction of DNA-conjugated aldehydes to diverse substituted tetrahydroquinolines and aminoimidazopyridines by Povarov and Groebke–Blackburn–Bienaymé reactions, respectively.

Rolling circle amplification shows a sinusoidal template length-dependent amplification bias

Bastian Joffroy, Yavuz O. Uca, Domen Prešern, Jonathan P. K. Doye, Thorsten L. Schmidt

Nucleic Acids Res. 2018, DOI:10.1093/nar/gkx1238

Small DNA circles can serve as templates for rolling circle amplification (RCA), which is a common and extremely robust amplification mechanism for nucleic acids. We discovered a strong template length-dependent amplification efficiency bias of RCA with the same periodicity as B-DNA.