PROTECs

PROTECs (Protein-Radical-Oxidation Targeting Enediyne Chimera) technology operates by delivering a reactive enediyne warhead to the vicinity of a target protein; the enediyne undergoes cycloaromatization to generate highly reactive free radicals, thereby inducing oxidative damage and degradation of the target protein through the proximity effect. During this process, free radical attacks modify protein side chains and backbones, leading to phenomena such as protein fragmentation, covalent cross-linking, unfolding, altered molecular interactions, and changes in protein turnover ^[1]. In this system, the enediyne functions as a radical-generating module, with its cycloaromatization producing diradical species. Studies utilizing Aβ core peptide hydrogels as a model have demonstrated that enediyne derivatives can cleave peptide chains; proposed mechanisms include hydrogen atom abstraction from the peptide chain or direct modification of the peptide backbone, which subsequently promotes peptide bond hydrolysis^[2]. This mechanism is directly relevant to research on Alzheimer's disease—where abnormal Aβ aggregation is a key pathological feature—as these enediyne studies have directly validated the process of free radical-mediated disruption of Aβ core peptides^[2].