Switching of peptide structure and biological activity using hydrophobic anchors

ORGN 323

Joris T. Meijer, j.meijer@science.ru.nl1, Inge Minten1, Dennis W. P. M. Löwik, d.lowik@science.ru.nl1, Bert E. W. Meijer, e.w.meijer@tue.nl2, and Jan C. M. van Hest, j.vanhest@science.ru.nl3. (1) Department of Organic Chemistry, Radboud University Nijmegen, Toernooiveld 1, Nijmegen, 6525 ED, Netherlands, (2) Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, PO Box 513, Eindhoven, NL-5600 MB, Netherlands, (3) Department of Organic Chemistry, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, Netherlands
The biological activity of peptides is directly related to their conformation. We have shown recently that we can stabilize a peptide in a biologically active or inactive conformation by the attachment of alkyl tails to the N and C terminus of the peptide. The introduction of a labile linker between the peptide and one of the hydrophobic anchors introduces a next level of control in manipulating peptide structure. By detachment of this hydrophobic anchor a peptide is allowed to take on its biologically active conformation. This methodology was applied to a cell penetrating peptide, TAT, which was anchored in a deactivated form on the surface of liposomes. After the peptide was allowed to take on its biologically active conformation a significantly increased cellular uptake of the liposomes was observed. This conformational switch therefore allows for otherwise unselective peptides to be activated at the desired target. This method is a potentially powerful addition to drug delivery.
 

Molecular Recognition and Self-Assembly
1:00 PM-5:00 PM, Monday, 11 September 2006 Moscone Center -- Room 132, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006