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Cell surface envelope protein transformation and membrane disruption by HIV-1 entry inhibitors
Dissertation   Open access

Cell surface envelope protein transformation and membrane disruption by HIV-1 entry inhibitors

Charles Gotuaco Ang
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2020
DOI:
https://doi.org/10.17918/00000025
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Abstract

Cell membranes HIV (Viruses)--Research Thiols Molecular Biology
This work examined transformations of the HIV-1 fusion protein Env and its anchoring membrane that can be subverted by lytic entry inhibitors to inactivate Env on viruses and cells. Two entry inhibitors were investigated: KR13 and M*DAVEI. KR13 is a chemically synthesized peptide triazole thiol (PTT) comprised of a CD4 binding site pharmacophore linked to a disulfide-targeting thiol, while M*DAVEI is a chimeric recombinant protein containing a gp120-glycan-binding lectin linked to Trp3, a gp41-binding fragment of Env's membrane proximal external region (MPER). Both inhibitors have previously been shown to cause virus lysis, indicating that they can trigger membrane disruption. Env-presenting cells were selected for these experiments to facilitate mechanistic studies and provide preliminary data for further cell-based studies.

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