Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix.

Abstract:

: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.

authors

Reshetnyak YK,Andreev OA,Lehnert U,Engelman DM

doi

10.1073/pnas.0601463103

subject

Has Abstract

pub_date

2006-04-25 00:00:00

pages

6460-5

issue

17

eissn

0027-8424

issn

1091-6490

pii

0601463103

journal_volume

103

pub_type

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