Eilatin Ru(II) complexes display anti-HIV activity and enantiomeric diversity in the binding of RNA

Nathan W. Luedtke; Judy S. Hwang; Edith C. Glazer; Dalia Gut; Moshe Kol; Yitzhak Tor

doi:10.1002/1439-7633(20020802)3:8<766::AID-CBIC766>3.0.CO;2-X

Eilatin Ru(II) complexes display anti-HIV activity and enantiomeric diversity in the binding of RNA

Nathan W. Luedtke, Judy S. Hwang, Edith C. Glazer, Dalia Gut, Moshe Kol, Yitzhak Tor

Chemistry

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

Abstract

Eilatin-containing octahedral ruthenium complexes inhibit HIV-1 replication in CD4+ HeLa cells and in human peripheral blood monocytes with IC₅₀ values of approximately 1 μM. Similar metal complexes that lack eilatin display 15-100-fold lower anti-HIV activities. [Ru(bpy)₂"pre-eilatin"]²⁺, a c omplex that contains a nonplanar analogue of eilatin, shows significantly lower nucleic acid binding and lower anti-HIV activity than eilatin complexes. This result indicates that the extended planar surface presented by eilatin is important for both activities. Rev peptide and ethidium bromide displacement assays are used to probe the nucleic acid affinity and specificity of Λ- and Δ-[Ru(bpy)₂eilatin]²⁺. Two HIV-1 RNA sites are compared and a significant binding preference for the Rev response element over the transactivation response region is found. Simple DNA duplexes show a consistent selectivity for Λ-[Ru(bpy)₂eilatin]²⁺ compared to Δ-[Ru(bpy)₂eilatin]²⁺, while RNAs show more diverse enantiomeric selectivities.

Original language	English
Pages (from-to)	766-771
Number of pages	6
Journal	ChemBioChem
Volume	3
Issue number	8
DOIs	https://doi.org/10.1002/1439-7633(20020802)3:8<766::AID-CBIC766>3.0.CO;2-X
State	Published - 2002

Keywords

DNA recognition
HIV
Medicinal chemistry
RNA recognition
Ruthenium

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/1439-7633(20020802)3:8<766::AID-CBIC766>3.0.CO;2-X

Cite this

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title = "Eilatin Ru(II) complexes display anti-HIV activity and enantiomeric diversity in the binding of RNA",

abstract = "Eilatin-containing octahedral ruthenium complexes inhibit HIV-1 replication in CD4+ HeLa cells and in human peripheral blood monocytes with IC50 values of approximately 1 μM. Similar metal complexes that lack eilatin display 15-100-fold lower anti-HIV activities. [Ru(bpy)2{"}pre-eilatin{"}]2+, a c omplex that contains a nonplanar analogue of eilatin, shows significantly lower nucleic acid binding and lower anti-HIV activity than eilatin complexes. This result indicates that the extended planar surface presented by eilatin is important for both activities. Rev peptide and ethidium bromide displacement assays are used to probe the nucleic acid affinity and specificity of Λ- and Δ-[Ru(bpy)2eilatin]2+. Two HIV-1 RNA sites are compared and a significant binding preference for the Rev response element over the transactivation response region is found. Simple DNA duplexes show a consistent selectivity for Λ-[Ru(bpy)2eilatin]2+ compared to Δ-[Ru(bpy)2eilatin]2+, while RNAs show more diverse enantiomeric selectivities.",

keywords = "DNA recognition, HIV, Medicinal chemistry, RNA recognition, Ruthenium",

author = "Luedtke, {Nathan W.} and Hwang, {Judy S.} and Glazer, {Edith C.} and Dalia Gut and Moshe Kol and Yitzhak Tor",

year = "2002",

doi = "10.1002/1439-7633(20020802)3:8<766::AID-CBIC766>3.0.CO;2-X",

language = "English",

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TY - JOUR

T1 - Eilatin Ru(II) complexes display anti-HIV activity and enantiomeric diversity in the binding of RNA

AU - Luedtke, Nathan W.

AU - Hwang, Judy S.

AU - Glazer, Edith C.

AU - Gut, Dalia

AU - Kol, Moshe

AU - Tor, Yitzhak

PY - 2002

Y1 - 2002

N2 - Eilatin-containing octahedral ruthenium complexes inhibit HIV-1 replication in CD4+ HeLa cells and in human peripheral blood monocytes with IC50 values of approximately 1 μM. Similar metal complexes that lack eilatin display 15-100-fold lower anti-HIV activities. [Ru(bpy)2"pre-eilatin"]2+, a c omplex that contains a nonplanar analogue of eilatin, shows significantly lower nucleic acid binding and lower anti-HIV activity than eilatin complexes. This result indicates that the extended planar surface presented by eilatin is important for both activities. Rev peptide and ethidium bromide displacement assays are used to probe the nucleic acid affinity and specificity of Λ- and Δ-[Ru(bpy)2eilatin]2+. Two HIV-1 RNA sites are compared and a significant binding preference for the Rev response element over the transactivation response region is found. Simple DNA duplexes show a consistent selectivity for Λ-[Ru(bpy)2eilatin]2+ compared to Δ-[Ru(bpy)2eilatin]2+, while RNAs show more diverse enantiomeric selectivities.

AB - Eilatin-containing octahedral ruthenium complexes inhibit HIV-1 replication in CD4+ HeLa cells and in human peripheral blood monocytes with IC50 values of approximately 1 μM. Similar metal complexes that lack eilatin display 15-100-fold lower anti-HIV activities. [Ru(bpy)2"pre-eilatin"]2+, a c omplex that contains a nonplanar analogue of eilatin, shows significantly lower nucleic acid binding and lower anti-HIV activity than eilatin complexes. This result indicates that the extended planar surface presented by eilatin is important for both activities. Rev peptide and ethidium bromide displacement assays are used to probe the nucleic acid affinity and specificity of Λ- and Δ-[Ru(bpy)2eilatin]2+. Two HIV-1 RNA sites are compared and a significant binding preference for the Rev response element over the transactivation response region is found. Simple DNA duplexes show a consistent selectivity for Λ-[Ru(bpy)2eilatin]2+ compared to Δ-[Ru(bpy)2eilatin]2+, while RNAs show more diverse enantiomeric selectivities.

KW - DNA recognition

KW - HIV

KW - Medicinal chemistry

KW - RNA recognition

KW - Ruthenium

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Eilatin Ru(II) complexes display anti-HIV activity and enantiomeric diversity in the binding of RNA

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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