Lipopeptides derived from HIV and SIV mimicking the prehairpin intermediate of gp41 on solid supported lipid bilayers.
We present a universal mimetic approach of the prehairpin intermediate of gp41, which represents the active drug target for fusion inhibitors of HIV (human immunodeficiency virus) and SIV (simian immunodeficiency virus) based on membrane anchored lipopeptides. For this purpose, we have in situ coupled terminal cysteine-modified peptides originating from the NHR of SIV and HIV to a maleimide-functionalized DOPC bilayer and monitored the interactions with potential antagonists of the trimer-of-hairpin conformation C34 and T20 peptides by means of atomic force microscopy and ellipsometry. FT-IR analysis in conjugation with CD-spectroscopy of hydrated N36-lipopeptides, incorporated in multilamellar bilayer stacks was employed to investigate peptide conformation prior to antagonist binding. In contrast to solution studies substantial secondary structure formation of S-N36 after in situ coupling to the bilayer was found. We could show that S-N36-lipopeptide-aggregates in bilayers were selectively able to bind T20 or the corresponding C-peptides (C34) and similar results could be achieved by using H-N36 lipopeptides. It was found that T20 binding to coiled coil S-N36 lipopeptide assemblies was fully reversible at elevated temperatures, while T20 binds irreversibly to H-N36 bundles.
Schuy
Steffen
S
Institute of Physical Chemistry, University of Göttingen, Germany.
Schäfer
Edith
E
Yoder
Nicholas C
NC
Kumar
Krishna
K
Vogel
Reiner
R
Janshoff
Andreas
A
D002942:Circular Dichroism; D006678:HIV / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism; D023581:HIV Fusion Inhibitors; D008051:Lipid Bilayers / Q000737:chemistry*; D055666:Lipopeptides / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D008051:Lipid Bilayers; D055666:Lipopeptides