Abstract: A polypeptide with a predominantly hydrophobic sequence long enough to span a membrane lipid bilayer as a transmembrane helix (TM) and comprising one or more dissociable groups inserts across a membrane spontaneously in a pH-dependant fashion placing one terminus inside cell. The polypeptide conjugated with various functional moieties delivers and accumulates them at cell membrane with low extracellular pH. The functional moiety conjugated with polypeptide terminus placed inside cell are translocated through the cell membrane in cytosol. The peptide and its variants or non-peptide analogs can be used to deliver therapeutic, prophylactic, diagnostic, imaging, gene regulation, cell regulation, or immunologic agents to or inside of cells in vitro or in vivo in tissue at low extracellular pH.
Type:
Application
Filed:
July 16, 2007
Publication date:
September 25, 2008
Applicant:
BOARD OF GOVERNORS FOR HIGHER EDUCATION, STATE OF RHODE ISLAND AND THE PROVIDE
Inventors:
Yana K. Reshetnyak, Oleg A. Andreev, Ursula Lehnert, Donald M. Engelmann