Technology

DEL, Advanced

The Power of DNA-Encoded Libraries

Imagine screening up to billions of molecules against your drug target in a single afternoon. DNA-Encoded Libraries (DEL) make this dream a reality. By tagging library members with unique DNA barcodes, a simple affinity screening can deliver hit compounds for beginning medicinal chemistry work without the need for developing a high-throughput activity assay. Read on to learn how DyNAbind’s proprietary technology platform is making DEL more powerful and reliable than ever before.

Library Composition

DyNAbind’s entire library collection was designed with one goal in mind – to generate only hits which are pharmaceutically relevant. We’ve leveraged over 50 years of medicinal chemistry experience to ensure that the physicochemical properties of our library members are ideal for development. Strict filtering in the construction process has removed promiscuous binders and known toxic substructures, while maintaining an average Tanimoto similarity of below 0.2, offering a massive compound diversity and opportunities to screen against nearly any target.

Library Composition

DyNAbind’s entire library collection was designed with one goal in mind – to generate only hits which are pharmaceutically relevant. We’ve leveraged over 50 years of medicinal chemistry experience to ensure that the physicochemical properties of our library members are ideal for development. Strict filtering in the construction process has removed promiscuous binders and known toxic substructures, while maintaining an average Tanimoto similarity of below 0.2, offering a massive compound diversity and opportunities to screen against nearly any target.

Dynamic Libraries

DyNAbind’s patented Dynamic Library technology represents a new philosophy in library design. While classical libraries build diversity only through opaque split-and-pool reactions with no quality control, Dynamic Libraries are built on two DNA strands which anneal together to present structural pairs to the target. The result is purified libraries which have transparent, trustworthy quality control. Creating chemical diversity through physical proximity reduces the need to conform with DNA-compatible chemical reactions, opening up new avenues of chemical space. Meanwhile, the Dynamic structural pairs reshuffle constantly in solution to generate optimized binding pairs which maximize target interaction. Dynamic Library design offers fewer, but more reliable hits and a clearer path to medicinal chemistry start points.

Dynamic Libraries

DyNAbind’s patented Dynamic Library technology represents a new philosophy in library design. While classical libraries build diversity only through opaque split-and-pool reactions with no quality control, Dynamic Libraries are built on two DNA strands which anneal together to present structural pairs to the target. The result is purified libraries which have transparent, trustworthy quality control. Creating chemical diversity through physical proximity reduces the need to conform with DNA-compatible chemical reactions, opening up new avenues of chemical space. Meanwhile, the Dynamic structural pairs reshuffle constantly in solution to generate optimized binding pairs which maximize target interaction. Dynamic Library design offers fewer, but more reliable hits and a clearer path to medicinal chemistry start points.

Path-Coding

When screening against a difficult target, every single detection counts. That’s why DyNAbind developed the Path-Coding system for encoding/decoding the DNA barcodes for our libraries. This proprietary system is a smarter way to encode libraries, offering built-in error detection and correction in library sequencing. This often overlooked aspect of DEL technology is of crucial importance: the Path-Coding system generates over 40% more usable reads, helping to separate signal from noise and locate the right molecules for your project.

Path-Coding

When screening against a difficult target, every single detection counts. That’s why DyNAbind developed the Path-Coding system for encoding/decoding the DNA barcodes for our libraries. This proprietary system is a smarter way to encode libraries, offering built-in error detection and correction in library sequencing. This often overlooked aspect of DEL technology is of crucial importance: the Path-Coding system generates over 40% more usable reads, helping to separate signal from noise and locate the right molecules for your project.

Binding Profiler

Once a screen is finished, the validation work begins. This used to mean mg scale resynthesis of hundreds of compounds to start probing functional activity. No longer, thanks to our Binding Profiler technology. This customized biosensor platform allows us to quickly perform kinetic hit validation on-DNA, revealing dissociation constants, on-rates and off-rates for the hits coming out of our selections. Fragment-based hits require no lead time, while our druglike compound libraries only require nanomole-scale resynthesis. Even dual-fragment hits can be validated in this way, without having to first link them off-DNA, saving potentially huge amounts of time for your medicinal chemistry team.

 

If you want to know more about the principles of our DNA-Encoded Library drug discovery technology, watch here our webinar.

Binding Profiler

Once a screen is finished, the validation work begins. This used to mean mg scale resynthesis of hundreds of compounds to start probing functional activity. No longer, thanks to our Binding Profiler technology. This customized biosensor platform allows us to quickly perform kinetic hit validation on-DNA, revealing dissociation constants, on-rates and off-rates for the hits coming out of our selections. Fragment-based hits require no lead time, while our druglike compound libraries only require nanomole-scale resynthesis. Even dual-fragment hits can be validated in this way, without having to first link them off-DNA, saving potentially huge amounts of time for your medicinal chemistry team.

 

If you want to know more about the principles of our DNA-Encoded Library drug discovery technology, watch here our webinar.