Discovery on Target 2023 – Boston

Poster sessions

Poster 1 Title: Increasing DNA Encoded Library Screening Resolution Using HT-SPR

Presenter: Noah T. Ditto, Technical Product Manager, Carterra

Location: P019

Abstract: DNA encoded library (DEL) technology has permitted substantial leaps in compound screening by enabling a more facile way to interrogate libraries and develop lead compounds. While a huge benefit to DEL technology is its reduction in the sheer number and tracking of discrete compounds through the screening process, it does come with a limitation in binding properties that can be gleaned for potential hits. In practice, from an initial screen numbering millions, the resulting thousands of hits are then reduced to around 50 compounds carried forward into downstream assays without any detailed characterization of their binding properties. These fundamental binding properties include kinetics as well as the target binding site. To address this resolution gap in DEL screening, demonstrated here is a technique to further characterize hits with improved resolution using high-throughput surface plasmon resonance (HT-SPR). HT-SPR characterizes the full kinetic profile for both weak and strong binders. Assay resolution can be further increased by inclusion of high-homology family members, truncated or mutated forms, binding partner disruption, etc., yielding a richer profile of lead candidates. With a screening capacity of thousands per week, HT-SPR affords a high-resolution technique that matches the throughput needs in this phase of discovery between the full library and a handful of leads. Additionally, this approach can work with any moiety having DNA attachment, including screening for targeted protein degraders (TPDs) and macrocycles.

Poster 2 Title: Selectivity and Cooperativity of PROTAC®s using HT-SPR

Presenter: Noah T. Ditto, Technical Product Manager, Carterra

Location: P021

Abstract: The unique heterobifunctional nature of PROTACs necessitates expanding the toolbox of characterization techniques to enable efficient drug discovery. Multiple warhead and linker combinations must be tested against the target protein(s) and ligases. Highlighted here is a strategy to characterize both binary and ternary kinetics for PROTACs against a panel of targets in parallel. Utilizing HT-SPR, a comprehensive assessment of both detailed binding selectivity and cooperativity can be obtained quickly using very small quantities of reagents.

Poster 3 Title: LSA^XT: Extending the Applications Space of HT-SPR

Presenter: Noah T. Ditto, Technical Product Manager, Carterra

Location: P020

Abstract: High-throughput surface plasmon resonance (HT-SPR) has transformed how real-time, label-free binding is deployed in modern, sophisticated drug discovery processes. These transformations have come from both substantial gains in throughput and reduced sample amounts. Described here is an expansion to the breadth of assays and applications HT-SPR can address by improvements in sensitivity and overall data quality, embodied in the new Carterra LSAXT. With these improvements, the versatility of HT-SPR can now be more easily leveraged in more challenging assay types such as PROTAC®s and kinase inhibitors.