Work

Selective Disruption of Early/Recycling Endosomes: Release of Disulfide-Linked Cargo Mediated by a N -Alkyl-3β-Cholesterylamine-Capped Peptide

Year: 2008

Type: article

Abstract: The use of endocytic uptake pathways to deliver poorly permeable molecules into mammalian cells is often plagued by entrapment and degradation of material in late endosomes and lysosomes. As a strategy to prevent the exposure of cargo to these highly hydrolytic membrane-sealed compartments, we synthesized derivatives of the membrane anchor N-alkyl-3beta-cholesterylamine that selectively target linked compounds to less hydrolytic early/recycling endosomes. By targeting a pH-dependent membrane-lytic dodecapeptide and a disulfide-linked fluorophore to these compartments in Chinese hamster ovary cells or Jurkat lymphocytes, membranes of early/recycling endosomes were selectively disrupted, resulting in cleavage of the disulfide and escape of the fluorophore into the cytosol and nucleus with low toxicity. The ability of appropriately designed N-alkyl-3beta-cholesterylamines to deliver cargo into and release disulfide-linked cargo from relatively nonhydrolytic early/recycling endosomes may be useful for the delivery of a variety of sensitive molecules into living mammalian cells.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja803380a

Authors: Qi Sun, Sutang Cai, Blake R. Peterson

Institutions: Pennsylvania State University, University of Kansas

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute