Project Details
Projekt
Exploring the potential of engineered enzyme families for selective N-alkylation of heteroarenes: A convergent synthesis approach with SAM analogs as intermediates
Applicant
Professor Dr. Stephan C. Hammer
Subject Area
Biological and Biomimetic Chemistry
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 510974120
The selective N-alkylation of heteroarenes could drastically shortcut synthesis of complex molecules, especially if two larger fragments could be coupled by selective C-N bond formation in a convergent approach. Here we propose to engineer, understand and apply enzyme families that synthesize and use S-adenosyl-L-methionine (SAM) analogs as intermediates for selective N-alkylation of heteroarenes. Our goal is to generate two enzyme families, namely sulfonium ion synthases that generate SAM analogs from S-adenosyl-L-homocysteine and "off the shelf" haloalkanes, and N-alkyltransferases that use these SAM analogs as co-substrates in selective C–N bond formations with heteroarene building blocks. This research i) aims to develop a catalytic method for a sought-after chemical transformation, ii) uses in silico mutagenesis for computational design of mutant libraries to systematically explore large regions of the amino acid sequence space, and iii) explores the potential of SAM analogs in convergent synthesis by coupling readily available fragments to complex molecules.
DFG Programme
Research Units
