Identification of Hsp90 Inhibitors with Anti-Plasmodium Activity.

Malaria remains a global health burden partly due to parasite resistance to first-line therapeutics. The molecular chaperone heat shock protein 90 (Hsp90) has emerged as an essential protein for blood-stage parasites, but details about its function during malaria's elusive liver stage are unclear. We used target-based screens to identify compounds that bind to and human Hsp90, which revealed insights into chemotypes with species-selective binding.

An Intrinsically Disordered Peptide Facilitates Non-Endosomal Cell Entry.

Many cell-penetrating peptides (CPPs) fold at cell surfaces, adopting α- or β-structure that enable their intracellular transport. However, the same structural folds that facilitate cellular entry can also elicit potent membrane-lytic activity, limiting their use in delivery applications. Further, a distinct CPP can enter cells through many mechanisms, often leading to endosomal entrapment.