The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.
Structure-based design, synthesis, and characterization of dual hotspot small-molecule HIV-1 entry inhibitors.
Judith M LaLonde; Young Do Kwon; David M Jones; Alexander W Sun; Joel R Courter; Takahiro Soeta; Toyoharu Kobayashi; Amy M Princiotto; Xueling Wu; Arne Schön; et al. (Profiled Author: Ernesto Freire)
Department of Chemistry, Bryn Mawr College, Bryn Mawr, Pennsylvania 19010, USA. firstname.lastname@example.org
Journal of medicinal chemistry 2012;55(9):4382-96.
Cellular infection by HIV-1 is initiated with a binding event between the viral envelope glycoprotein gp120 and the cellular receptor protein CD4. The CD4-gp120 interface is dominated by two hotspots: a hydrophobic gp120 cavity capped by Phe43(CD4) and an electrostatic interaction between residues Arg59(CD4) and Asp368(gp120). The CD4 mimetic small-molecule NBD-556 (1) binds within the gp120 cavity; however, 1 and related congeners demonstrate limited viral neutralization breadth. Herein, we report the design, synthesis, characterization, and X-ray structures of gp120 in complex with small molecules that simultaneously engage both binding hotspots. The compounds specifically inhibit viral infection of 42 tier 2 clades B and C viruses and are shown to be antagonists of entry into CD4-negative cells. Dual hotspot design thus provides both a means to enhance neutralization potency of HIV-1 entry inhibitors and a novel structural paradigm for inhibiting the CD4-gp120 protein-protein interaction.
This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.
Evan T Brower; Arne Schön; Ernesto FreireBiochemistry 2010;49(11):2359-67.
Navid Madani; Arne Schön; Amy M Princiotto; Judith M Lalonde; Joel R Courter; Takahiro Soeta; Danny Ng; Liping Wang; Evan T Brower; Shi-Hua Xiang; et al.Structure (London, England : 1993) 2008;16(11):1689-701.
M L Bellows; M S Taylor; P A Cole; L Shen; R F Siliciano; H K Fung; C A FloudasBiophysical journal 2010;99(10):3445-53.
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