Supramolecular Control of Enzyme Activity through Cucurbit[8]uril-Mediated Dimerization

摘要

Protein dimerization is a ubiquitous mechanism to regulate protein activity in a broad range of biological processes including receptor clustering, signal transduction, and apop-tosis. Molecular control over these processes is critical to elucidate and perturb the molecular mechanisms of the proteins involved. To be amenable to small-molecule regulation, proteins of interest typically require substantial protein engineering and introduction of additional protein domains that bind the small molecule. Control over protein dimerization by using a small, genetically encoded, peptide motif is a highly attractive target in this respect, as a short peptide motif would impose the smallest possible influence on the protein of study. Small molecules do not typically bind to short peptide fragments, however.