A Biochemical/Biophysical Assay Dyad for HTS-Compatible Triaging of Inhibitors of the HIV-1 Nef/Hck SH3 Interaction
Sebastian Breuer1, *, Sheryll Espinola2, Xavier Morelli3, Bruce E Torbett1, Stefan T Arold4, 5, Ingo H Engels2
Identifiers and Pagination:Year: 2013
First Page: 16
Last Page: 20
Publisher Id: CCGTM-7-16
Article History:Received Date: 18/3/2013
Revision Received Date: 9/5/2013
Acceptance Date: 20/5/2013
Electronic publication date: 26/7/2013
Collection year: 2013
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
The current treatment regimens for HIV include over 20 anti-retrovirals. However, adverse drug effects and the emergence of drug resistance necessitates the continued improvement of the existing drug classes as well as the development of novel drugs that target as yet therapeutically unexploited viral and cellular pathways. Here we demonstrate a strategy for the discovery of protein-protein interaction inhibitors of the viral pathogenicity factor HIV-1 Nef and its interaction with the host factor SH3. A combination of a time-resolved fluorescence resonance energy resonance energy transfer-based assay and a label-free resonant waveguide grating-based assay was optimized for high-throughput screening formats.