A benzylic linker promotes methyltransferase catalyzed norbornene transfer for rapid bioorthogonal tetrazine ligation

Autor:	Nils Muthmann, Dennis Reichert, Lea Anhäuser, Fabian Muttach, Andrea Rentmeister
Rok vydání:	2017
Předmět:	010405 organic chemistry General Chemistry Alkylation 010402 general chemistry 01 natural sciences Combinatorial chemistry 0104 chemical sciences Tetrazine chemistry.chemical_compound chemistry Nucleic acid Organic chemistry Moiety Bioorthogonal chemistry Linker DNA Norbornene
Zdroj:	Chemical Science. 8:7947-7953
ISSN:	2041-6539 2041-6520
DOI:	10.1039/c7sc03631k
Popis:	Site-specific alkylation of complex biomolecules is critical for late-stage product diversification as well as post-synthetic labeling and manipulation of proteins and nucleic acids. Promiscuous methyltransferases in combination with analogs of S-adenosyl-L-methionine (AdoMet) can functionalize all major classes of biomolecules. We show that benzylic moieties are transferred by Ecm1 with higher catalytic efficiency than the natural AdoMet. A relative specificity of up to 80% is achieved when a norbornene moiety is placed in para-position, enabling for the first time enzymatic norbornene transfer to specific positions in DNA and RNA— even in cell lysate. Subsequent tetrazine ligation of the stable norbornene moiety is fast, efficient, biocompatible and – in combination with an appropriate tetrazine – fluorogenic.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::a9a5b6ca04143418e2ad712f2c5bbc4d https://doi.org/10.1039/c7sc03631k Zobrazit plný text záznamu