ArticleJournal of medicinal chemistry2013
Interfacial cavity filling to optimize CD4-mimetic miniprotein interactions with HIV-1 surface glycoprotein.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review.Viruses · 2023Pooled it
- HIV-1 Entry and Membrane Fusion Inhibitors.Viruses · 2021Review
- In Silico Identification of Novel Aromatic Compounds as Potential HIV-1 Entry Inhibitors Mimicking Cellular Receptor CD4.Viruses · 2019Article
- Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41.Viruses · 2019Review
- Hydrogenolytic cleavage of naphthylmethyl ethers in the presence of sulfides.Carbohydrate research · 2017Article
- Computational identification of novel entry inhibitor scaffolds mimicking primary receptor CD4 of HIV-1 gp120.Journal of molecular modeling · 2017Article
- CD4-mimetic sulfopeptide conjugates display sub-nanomolar anti-HIV-1 activity and protect macaques against a SHIV162P3 vaginal challenge.Scientific reports · 2016Article
- Synthesis, antiviral activity and resistance of a novel small molecule HIV-1 entry inhibitor.Bioorganic & medicinal chemistry · 2015Article
- Macrocyclic Envelope Glycoprotein Antagonists that Irreversibly Inactivate HIV-1 before Host Cell Encounter.Journal of medicinal chemistry · 2015Article
- HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth.Expert opinion on therapeutic targets · 2015Review
- Coevolution Analysis of HIV-1 Envelope Glycoprotein Complex.PloS one · 2015Article
- Redesigning protein cavities as a strategy for increasing affinity in protein-protein interaction: interferon- γ receptor 1 as a model.BioMed research international · 2015Article
- Crystal structures of HIV-1 gp120 envelope glycoprotein in complex with NBD analogues that target the CD4-binding site.PloS one · 2014Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Ligand affinities can be optimized by interfacial cavity filling. A hollow (Phe43 cavity) between HIV-1 surface glycoprotein (gp120) and cluster of differentiation 4 (CD4) receptor extends beyond residue phenylalanine 43 of CD4 and cannot be fully accessed by natural amino acids. To increase HIV-1 gp120 affinity for a family of CD4-mimetic miniproteins (miniCD4s), we targeted the gp120 Phe43 cavity with 11 non-natural phenylalanine derivatives, introduced into a miniCD4 named M48 (1). The best derivative, named M48U12 (13), bound HIV-1 YU2 gp120 with 8 pM affinity and showed potent HIV-1 neutralization. It contained a methylcyclohexyl derivative of 4-aminophenylalanine, and its cocrystal structure with gp120 revealed the cyclohexane ring buried within the gp120 hydrophobic core but able to assume multiple orientations in the binding pocket, and the aniline nitrogen potentially providing a focus for further improvement. Altogether, the results provide a framework for filling the interfacial Phe43 cavity to enhance miniCD4 affinity.
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