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OHSU # 2757 — Clickable, photoactivatable NAD+ analogues as probes for PARP and other NAD+-binding targets

Summary

Researchers at OHSU have developed a screening platform for identification of proteins regulated by PARPs, which relies on a novel bi-functional NAD analog containing a photo-reactive group for crosslinking to binding targets and a click tag for their identification. This tool can be used to efficiently screen cell lysates to uncover novel PARP biology for translational research.

Technology Overview

PARP enzymes regulate diverse cellular functions through a post-translational modification involving the transfer of ADP-ribose moiety from an NAD molecule to a targeted protein. PARP inhibitors are promising anti-cancer drugs, but the full therapeutic potential of PARP biology is unknown due to the fact that the binding targets of many PARPs have yet to be identified. The laboratory of Michael Cohen has developed a novel competition-based assay using a clickable small molecule NAD+-like probe that binds to all PARP family members. This molecule can be used with any cell line of interest and the light-activated crosslinking component offers the ability to selectively identify PARP binding targets at specific experimental timepoints. Following photo-activation, the click tag is also transferred to the target protein; therefore, this novel molecule provides the dual advantage of enhanced temporal resolution and increased efficiency for identification of PARP binding partners in translational research.

Licensing Opportunity 

This technology is available for licensing.

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Patents

Filed United States
Published United States WO 2021/262548 A1
Published United States US 2023/0212213 A1

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