| Synthesis and anti-HIV activity of trivalent CD4-mimetic miniproteins. | |
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MedLine Citation:
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PMID: 17412600 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A series of trivalent CD4-mimetic miniproteins was synthesized, in which three CD4M9 miniprotein moieties were tethered on a threefold-symmetric scaffold. The trivalent miniproteins were designed to target the CD4-binding sites displayed in the trimeric gp120 complex of HIV-1. The synthesis takes advantage of the highly efficient ligation between a cysteine-tagged CD4M9 miniprotein and a suitable trivalent maleimide that varied in the nature and length of spacer. Antiviral assay revealed that most of the synthetic trivalent miniproteins demonstrated significantly enhanced anti-HIV activities over the monomeric CD4M9 against both R5- and X4-tropic viruses, indicating the beneficial multivalent effects. One compound that possesses a hydrophobic linker was shown to be 140-fold more active than CD4M9 against HIV-1(Bal) infection, implicating a positive contribution of the lipid portion to the antiviral activity. It was also found that most of the trivalent miniproteins showed comparable anti-HIV activities in comparison with a typical bivalent miniprotein, regardless of the length of the linker. The results implicate a novel mechanism of the interactions between the multivalent inhibitors and the trimeric gp120 complex. |
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Authors:
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Hengguang Li; Yongjun Guan; Agnieszka Szczepanska; Antonio J Moreno-Vargas; Ana T Carmona; Inmaculada Robina; George K Lewis; Lai-Xi Wang |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-03-24 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry Volume: 15 ISSN: 0968-0896 ISO Abbreviation: Bioorg. Med. Chem. Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-05-08 Completed Date: 2007-07-30 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 9413298 Medline TA: Bioorg Med Chem Country: England |
Other Details:
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Languages: eng Pagination: 4220-8 Citation Subset: IM |
Affiliation:
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Institute of Human Virology, University of Maryland, Baltimore, MD 21201, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anti-HIV Agents
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chemical synthesis*,
pharmacology* Antigens, CD4 / chemistry* Cell Line Humans Magnetic Resonance Spectroscopy Molecular Mimicry* Spectrometry, Mass, Electrospray Ionization |
| Grant Support | |
ID/Acronym/Agency:
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AI51235/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; 0/Antigens, CD4 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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