Research expertise and methodologies

• Design and synthesis of DNA-encoded chemical libraries, including DNA-compatible multistep synthesis and follow-up synthesis of off-DNA analogues.
• Synthetic organic electrochemistry and electrocatalysis: constant-current electrolysis, undivided-cell electrosynthesis, C–H functionalization and electrochemical cascade reactions.
• Organic and medicinal chemistry, small-molecule library synthesis and late-stage functionalization of bioactive compounds.
• Reaction optimization and mechanistic studies using LC-MS, HPLC, NMR and cyclic voltammetry, complemented by physical-organic and computational studies through collaboration.
  

Ongoing research projects

DNA-encoded libraries for antibacterial discovery

DNA-encoded library technology enables very large chemical spaces to be explored using affinity-based selections with comparatively modest experimental infrastructure. Within the Uppsala Antibiotic Center, we use this approach to identify new chemical starting points for antibacterial drug discovery. A current project focuses on the design and screening of DELs against LpxH, an essential enzyme in lipid A biosynthesis and an attractive target for new agents against Gram-negative bacteria. The work combines library design and synthesis with target-based selection and follow-up medicinal chemistry.

Expanding the synthetic toolbox for DNA-encoded libraries

A major limitation of DEL technology is the restricted set of chemical reactions that can be performed without damaging the DNA barcode. We therefore develop new DNA-compatible transformations and orthogonal protecting-group strategies that enable access to more diverse, drug-like molecular architectures. Current efforts include multistep on-DNA synthesis and new amine protection/deprotection chemistry, as well as the construction of chemically diverse peptide-like libraries. Expanding the accessible chemistry increases the likelihood of finding useful starting points against challenging antimicrobial targets.

Electrochemical synthesis for medicinal chemistry

In parallel, our group develops sustainable electrochemical methods for the rapid synthesis and diversification of medicinally relevant molecules. Recent work has focused on selective C–H halogenation, acyloxylation and one-pot electrochemical cascade reactions that operate under mild conditions and often avoid stoichiometric oxidants, additional redox reagents or supporting electrolytes. These methods provide practical tools for late-stage functionalization and analogue generation and can complement DEL-based hit discovery by enabling efficient synthesis of follow-up compounds around promising antibacterial chemotypes.

Key Publications

1. Ponra S., Sitdikov R., Aman H., Calis A., Laczkó G., Rouffeteau V., Vitale M.R., Pápai I., Verho O. (2026) One-pot amidation/C–H halogenation by an efficient electrochemical cascade. Angewandte Chemie International Edition, 65(19). https://doi.org/10.1002/anie.9028210

2. Ponra S., Peter Z., Sheikh M.W., Eriksson L., Verho O. (2026) Electrochemical cascade N-acylation and C–H halogenation of azaindoles. ChemElectroChem. https://doi.org/10.1002/celc.70207

3. Ponra S., Verho O. (2026) Green electrochemistry-enabled one-pot synthesis of halogenated amides from readily available carboxylic acids. RSC Advances. https://doi.org/10.1039/D6RA04649E

4. Sitdikov R., Nikolaienko P., Meyer L., Verho O. (2025) Cobaltaelectro-catalyzed C–H acyloxylation of aromatic and vinylic amide derivatives at room temperature. Chemical Communications, 61, 16946–16949. https://doi.org/10.1039/D5CC04394H

5. Ponra S., Sitdikov R., Calis A., Verho O. (2025) Regioselective palladaelectro-catalyzed chlorination of arenes in an undivided cell. Advanced Synthesis & Catalysis, 367, e202401298. https://doi.org/10.1002/adsc.202401298

6. Akaberi D., Pourghasemi Lati M., Krambrich J., Berger J., Neilsen G., Strandback E., Turunen S.P., Wannberg J., Gullberg H., Moche M., Chinthakindi P.K., Nyman T., Sarafianos S.G., Sandström A., Järhult J.D., Sandberg K., Lundkvist Å., Verho O., Lennerstrand J. (2024) Identification of novel and potent inhibitors of SARS-CoV-2 main protease from DNA-encoded chemical libraries. Antimicrobial Agents and Chemotherapy, 68(10), e0090924. https://doi.org/10.1128/aac.00909-24