DEL Hit Validation
On-DNA hit confirmation with full kinetic characterization
The off-DNA bottleneck
After DEL selection and NGS readout, DNA barcodes are decoded to identify enriched hits. But barcodes encode the building blocks used during synthesis, not the chemistry that actually happened.
All products from the same synthesis step carry the same barcode. If the real binder is a side product, sequencing will never reveal it.
The conventional approach is off-DNA resynthesis: rebuild the assumed hit from scratch using different chemistry (organic solvents, different conditions). This takes 2–4 months, is expensive, and produces a different molecular mixture than the original library synthesis.
The result: high attrition rates, wasted medicinal chemistry effort, and side-product binders lost forever.
Why off-DNA resynthesis fails
| Chemistry | Different from library synthesis |
| Side reactions | Different – original mixture lost |
| Side-product hits | Invisible – cannot be discovered |
| Timeline | 2–4 months per compound |
| False positive rate | High – wrong molecule resynthesized |
See the MACS Matchmaker DEL workflow
From NGS readout to kinetic data
A streamlined four-step protocol validates your DEL hits with full kinetic characterization.
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1
IdentifyNGS identifies enriched barcodes from DEL affinity selection |
2
ResynthesizeOn-DNA resynthesis under the same conditions as library synthesis |
3
ImmobilizeDNA-directed immobilization via Ligation Kit on oligo sensorchip |
4
CharacterizeFull kinetic profiling (ka, kd, KD) on the MACS Matchmaker in ~90 min |
The MACS Matchmaker solution
Resynthesize hits on-DNA under the same conditions as library synthesis. Validate binding directly on the oligo sensorchip.
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1
Chemistry
Same conditions
On-DNA resynthesis under original library conditions. Same side reactions, same molecular mixture as the screen.
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2
Discovery
Side-product recovery
Higher-quantity resynthesis enables MS identification of real binders that off-DNA resynthesis misses entirely.
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3
Kinetics
Full characterization
Complete ka, kd, KD determination in approximately 90 minutes per chip.
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4
Throughput
64 hits per chip
8×8 mologram array for parallel measurement. No sequential testing required.
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5
Speed
4 weeks, not 4 months
Reduce the validation bottleneck from months of off-DNA resynthesis to weeks.
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6
IP Protection
No sequence disclosure
DNA Ligation Kit protects proprietary sequences during immobilization on the oligo sensorchip.
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Validate your DEL hits
Send us your on-DNA compounds and receive full kinetic data within weeks.