Discovery on Target 2026: From Living-Cell GPCRs to On-DNA DEL Hits

About the talk

Recorded at Discovery on Target 2026 in Boston on September 30, 2026, in the Lead Generation Strategies track. In 23 minutes, Dr. Volker Gatterdam shows where focal molography measures what purified-protein assays cannot reach.

What the talk covers

• The measurement principle. 64 molograms per chip, each a line structure of about 200 nm in which the ridges carry the ligand and the grooves act as a built-in reference. Only specific binding produces a diffractive signal, so nonspecific binding and bulk refractive index changes cancel out. Example data include single-cycle kinetics in buffer and in 50 percent human serum.
• GPCRs in living cells. A binder on the mologram structures the receptor inside the cell membrane, which copies the diffractive pattern into the living cell. Shown on the beta-2 adrenergic receptor: compound addition activated the receptor and beta-arrestin recruitment was followed label-free, while activating a different GPCR in the same cells produced no signal.
• Antibody panels. Polyreactivity profiling against nucleic acids and plasma carrier proteins in about one hour per run, plasma protein binding measured in crude donor plasma with an apparent affinity for plasma recruitment, plus classical Fc gamma receptor and FcRn panels.
• On-DNA hit validation for DNA-encoded libraries. Protocols that make the DNA tag of DEL compounds compatible with the oligonucleotide chip, so on-rates and off-rates are measured before resynthesis. Up to 64 single-cycle traces per chip narrow a hit list down to the compounds worth making.

Immobilization uses DNA-directed immobilization (DDI): ligands carry a complementary oligonucleotide and assemble themselves on the chip, with no spotting step and no complex fluidics.