Nicolas Winssinger

Peptide nucleic acid sits in an unusual place: a nucleic acid that recognizes sequence by Watson–Crick pairing, built on a peptide backbone that chemists can make on a synthesizer. Nicolas Winssinger has spent two decades showing what that hybrid can do. At the University of Geneva, where he is Professor in the Department of Organic Chemistry, his laboratory uses PNA as a programmable tag, letting hybridization instructions dictate which molecules assemble, how far apart they sit, and when a reaction fires.

One line of that work rebuilt how encoded libraries are made. By tagging small molecules with PNA rather than DNA, Winssinger’s group sidestepped the constraints of split-and-pool synthesis and produced libraries that can be read out on microarrays or displayed combinatorially on DNA templates. The approach yielded the largest glycan array reported at the time, the first covalent bromodomain inhibitor suitable for proteomic profiling, and an assembly that outcompetes HIV binding to dendritic cells. Because the templates are amplifiable by PCR, the system supports iterative cycles of translation, selection and amplification, a chemical analog of evolution.

A second line turns hybridization into a trigger. The group has developed DNA- and RNA-templated reactions that run inside living cells, bringing two PNA strands together on a nucleic acid template so that a reaction proceeds only where the target sequence is present. The chemistry includes the first azide-based profluorophores and ruthenium photocatalysts that perform bioorthogonal transformations in cells and in live zebrafish. In a further twist, the lab has coupled bioluminescence to those photocatalysts, using light generated by the system itself to drive abiotic chemistry in vivo.

The peptide thread runs through the newest work. Short PNA–peptide conjugates that hybridize into a defined fold hold their peptide segments in constrained conformations, producing self-assembled proteomimetics with antibody-like binding from building blocks a fraction of the size.

Winssinger studied chemistry at Tufts University and completed his Ph.D. with K. C. Nicolaou at The Scripps Research Institute in 2000, working on the total synthesis of vancomycin and the epothilones, followed by postdoctoral research with Peter Schultz at Scripps. He joined the University of Strasbourg in 2002, became full professor in 2005, was elected to the Institut Universitaire de France, and moved to Geneva in 2012. In 2026 he was named a co-recipient of the Klaus Grohe Prize, one of Europe’s principal distinctions in medicinal chemistry.

Few programs illustrate the symposium’s theme more directly: a peptide backbone, used as the instruction set for chemistry that happens inside a living animal.