Abstract
Active intracellular transport is a central mechanism in cell biology, directed by a limited set of naturally occurring signaling peptides. Here, we report the first nonpeptide moiety that recruits intracellular transport machinery for nuclear targeting. Proteins synthetically modified with a simple aromatic boronate motif are actively trafficked to the nucleus via the importin α/β pathway. Significantly, proteins too large to passively diffuse through nuclear pores were readily imported into the nucleus through this boronate-mediated pathway. The use of this simple motif to provide active intracellular targeting provides a promising strategy for directing subcellular localization for therapeutic and fundamental applications.