Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix.
We have previously observed the spontaneous, pH-dependent insertion of a water-soluble peptide to form a helix across lipid bilayers [Hunt, J. F., Rath, P., Rothschild, K. J. & Engelman, D. M. (1997) Biochemistry 36, 15177-15192]. We now use a related peptide, pH (low) insertion peptide, to translocate cargo molecules attached to its C terminus across the plasma membranes of living cells. Translocation is selective for low pH, and various types of cargo molecules attached by disulfides can be released by reduction in the cytoplasm, including peptide nucleic acids, a cyclic peptide (phalloidin), and organic compounds. Because a high extracellular acidity is characteristic of a variety of pathological conditions (such as tumors, infarcts, stroke-afflicted tissue, atherosclerotic lesions, sites of inflammation or infection, or damaged tissue resulting from trauma) or might be created artificially, pH (low) insertion peptide may prove a useful tool for selective delivery of agents for drug therapy, diagnostic imaging, genetic control, or cell regulation.
Reshetnyak
Yana K
YK
Department of Molecular Biophysics and Biochemistry, Yale University, P.O. Box 208114, New Haven, CT 06520, USA. reshetnyak@mail.uri.edu
Andreev
Oleg A
OA
Lehnert
Ursula
U
Engelman
Donald M
DM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001693:Biological Transport, Active; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary
D008051:Lipid Bilayers; D008565:Membrane Proteins; D020135:Peptide Nucleic Acids; D010455:Peptides