Document Type
Article
Date of Original Version
4-25-2006
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.
Citation/Publisher Attribution
Reshetnyak, Y. K., Andreev, O. A., Lehnert, U., & Engelman, D. M. (2006). Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix. Proceedings of the National Academy of Sciences, 103(17), 6460-6465. doi: 10.1073/pnas.0601463103
Available at: https://doi.org/10.1073/pnas.0601463103
Terms of Use
All rights reserved under copyright.
Publisher Statement
Freely available online through the PNAS open access option. © 2006 by The National Academy of Sciences of the USA