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Int J Med Sci 2008; 5(5):230-239. doi:10.7150/ijms.5.230

Research Paper

HIV-1 Capsid Assembly Inhibitor (CAI) Peptide: Structural Preferences and Delivery into Human Embryonic Lung Cells and Lymphocytes

Klaus Braun1, Martin Frank2, Rüdiger Pipkorn3, Jennifer Reed4, Herbert Spring5, Jürgen Debus6, Bernd Didinger6, Claus-Wilhelm von der Lieth2, Manfred Wiessler1, Waldemar Waldeck7

1. German Cancer Research Center, Division of Molecular Toxicology, INF 280, D-69120 Heidelberg, Germany
2. German Cancer Research Center, Division Central Spectroscopy B090, INF 280, D-69120 Heidelberg, Germany
3. German Cancer Research Center, Core Facility Peptide Synthesis, INF 580, D-69120 Heidelberg, Germany
4. German Cancer Research Center, Biomolecular Mechanisms, INF 280, D-69120 Heidelberg, Germany
5. German Cancer Research Center, Research Group Structural Biochemistry, INF 280, D-69120 Heidelberg, Germany
6. University of Heidelberg, Radiation Oncology, INF 110, D-69120 Heidelberg
7. German Cancer Research Center, Division of Biophysics of Macromolecules, INF 580, D-69120 Heidelberg, Germany

Abstract

The Human immunodeficiency virus 1 derived capsid assembly inhibitor peptide (HIV-1 CAI-peptide) is a promising lead candidate for anti-HIV drug development. Its drawback, however, is that it cannot permeate cells directly. Here we report the transport of the pharmacologically active CAI-peptide into human lymphocytes and Human Embryonic Lung cells (HEL) using the BioShuttle platform. Generally, the transfer of pharmacologically active substances across membranes, demonstrated by confocal laser scanning microscopy (CLSM), could lead to a loss of function by changing the molecule's structure. Molecular dynamics (MD) simulations and circular dichroism (CD) studies suggest that the CAI-peptide has an intrinsic capacity to form a helical structure, which seems to be critical for the pharmacological effect as revealed by intensive docking calculations and comparison with control peptides. This coupling of the CAI-peptide to a BioShuttle-molecule additionally improved its solubility. Under the conditions described, the HIV-1 CAI peptide was transported into living cells and could be localized in the vicinity of the mitochondria.

Keywords: BioShuttle, Capsid Assembly Inhibitors, Drug Delivery, HIV-Drug Development

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How to cite this article:
Braun K, Frank M, Pipkorn R, Reed J, Spring H, Debus J, Didinger B, von der Lieth CW, Wiessler M, Waldeck W. HIV-1 Capsid Assembly Inhibitor (CAI) Peptide: Structural Preferences and Delivery into Human Embryonic Lung Cells and Lymphocytes. Int J Med Sci 2008; 5(5):230-239. doi:10.7150/ijms.5.230. Available from http://www.medsci.org/v05p0230.htm