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NOBEL PRIZE 2026

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NIHNATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

Development of phosphorylation editing chimeras using kinase inhibitors

Completed
Institution
BROAD INSTITUTE, INC., MA
Principal investigator
Amit Choudhary
Funding
$210K
Duration
2024–2026
Open portfolio

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Abstract

PROJECT SUMMARY Protein post-translational modifications (PTMs) can activate, inhibit, or modify protein’s function. Small molecules that inhibit enzymes that induce PTMs (e.g., kinases for phosphorylation) are available in abundance, but methods to induce a given PTM of any protein on demand are challenging to develop. We propose to develop a new class of small molecules which will induce protein phosphorylation by using a kinase inhibitor to recruit the given kinase to phosphorylate a neo-substrate. These molecules will be formed by joining a small-molecule kinase inhibitor with a small-molecule binder of the target protein so that an active kinase is brought into proximity to the target protein to initiate phosphorylation. 1

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NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESR21Chemical Biology and Probes Study Section[CBP]phosphorylationinducesmall moleculeskinase inhibitorsmall-moleculekinaseptmstarget protein

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