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