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Iron(II) supramolecular helicates interfere with the HIV-1 Tat-TAR RNA interaction critical for viral replication.

Malina J, Hannon MJ, Brabec V - Sci Rep (2016)

Bottom Line: The interaction between the HIV-1 transactivator protein Tat and TAR (transactivation responsive region) RNA, plays a critical role in HIV-1 transcription.The results demonstrate that iron(II) supramolecular helicates inhibit Tat-TAR interaction at nanomolar concentrations by binding to TAR RNA.These studies provide a new insight into the biological potential of metallosupramolecular helicates.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, CZ-61265 Brno, Czech Republic.

ABSTRACT
The interaction between the HIV-1 transactivator protein Tat and TAR (transactivation responsive region) RNA, plays a critical role in HIV-1 transcription. Iron(II) supramolecular helicates were evaluated for their in vitro activity to inhibit Tat-TAR RNA interaction using UV melting studies, electrophoretic mobility shift assay, and RNase A footprinting. The results demonstrate that iron(II) supramolecular helicates inhibit Tat-TAR interaction at nanomolar concentrations by binding to TAR RNA. These studies provide a new insight into the biological potential of metallosupramolecular helicates.

No MeSH data available.


Related in: MedlinePlus

Binding of the helicates to TAR RNA.Autoradiogram of the gel run at 5 °C showing binding of the helicates to TAR RNA (2 μM). Lane C: TAR-RNA in the absence of the helicates. Lanes 1–6: TAR RNA mixed with M-[Fe2L3]Cl4 at 0.25:1, 0.5:1, 0.75:1, 1:1, 1.5:1 and 2:1 (helicate:TAR RNA) ratios, respectively. Lanes 7–12: TAR RNA mixed with P-[Fe2L3]Cl4 at 0.25:1, 0.5:1, 0.75:1, 1:1, 1.5:1 and 2:1 (helicate:TAR RNA) ratios, respectively.
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f2: Binding of the helicates to TAR RNA.Autoradiogram of the gel run at 5 °C showing binding of the helicates to TAR RNA (2 μM). Lane C: TAR-RNA in the absence of the helicates. Lanes 1–6: TAR RNA mixed with M-[Fe2L3]Cl4 at 0.25:1, 0.5:1, 0.75:1, 1:1, 1.5:1 and 2:1 (helicate:TAR RNA) ratios, respectively. Lanes 7–12: TAR RNA mixed with P-[Fe2L3]Cl4 at 0.25:1, 0.5:1, 0.75:1, 1:1, 1.5:1 and 2:1 (helicate:TAR RNA) ratios, respectively.

Mentions: An electrophoretic mobility shift assay (EMSA) was used to explore the stability of the helicate:TAR RNA complex. The autoradiogram of the electrophoresis gel run at 5 °C (Fig. 2) shows the interaction of the TAR RNA with increasing concentrations of M- and P-[Fe2L3]Cl4. It can be seen that a new, more slowly migrating band indicating the formation of the helicate:TAR RNA complex appears in the gel in the presence of the helicates.


Iron(II) supramolecular helicates interfere with the HIV-1 Tat-TAR RNA interaction critical for viral replication.

Malina J, Hannon MJ, Brabec V - Sci Rep (2016)

Binding of the helicates to TAR RNA.Autoradiogram of the gel run at 5 °C showing binding of the helicates to TAR RNA (2 μM). Lane C: TAR-RNA in the absence of the helicates. Lanes 1–6: TAR RNA mixed with M-[Fe2L3]Cl4 at 0.25:1, 0.5:1, 0.75:1, 1:1, 1.5:1 and 2:1 (helicate:TAR RNA) ratios, respectively. Lanes 7–12: TAR RNA mixed with P-[Fe2L3]Cl4 at 0.25:1, 0.5:1, 0.75:1, 1:1, 1.5:1 and 2:1 (helicate:TAR RNA) ratios, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940744&req=5

f2: Binding of the helicates to TAR RNA.Autoradiogram of the gel run at 5 °C showing binding of the helicates to TAR RNA (2 μM). Lane C: TAR-RNA in the absence of the helicates. Lanes 1–6: TAR RNA mixed with M-[Fe2L3]Cl4 at 0.25:1, 0.5:1, 0.75:1, 1:1, 1.5:1 and 2:1 (helicate:TAR RNA) ratios, respectively. Lanes 7–12: TAR RNA mixed with P-[Fe2L3]Cl4 at 0.25:1, 0.5:1, 0.75:1, 1:1, 1.5:1 and 2:1 (helicate:TAR RNA) ratios, respectively.
Mentions: An electrophoretic mobility shift assay (EMSA) was used to explore the stability of the helicate:TAR RNA complex. The autoradiogram of the electrophoresis gel run at 5 °C (Fig. 2) shows the interaction of the TAR RNA with increasing concentrations of M- and P-[Fe2L3]Cl4. It can be seen that a new, more slowly migrating band indicating the formation of the helicate:TAR RNA complex appears in the gel in the presence of the helicates.

Bottom Line: The interaction between the HIV-1 transactivator protein Tat and TAR (transactivation responsive region) RNA, plays a critical role in HIV-1 transcription.The results demonstrate that iron(II) supramolecular helicates inhibit Tat-TAR interaction at nanomolar concentrations by binding to TAR RNA.These studies provide a new insight into the biological potential of metallosupramolecular helicates.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, CZ-61265 Brno, Czech Republic.

ABSTRACT
The interaction between the HIV-1 transactivator protein Tat and TAR (transactivation responsive region) RNA, plays a critical role in HIV-1 transcription. Iron(II) supramolecular helicates were evaluated for their in vitro activity to inhibit Tat-TAR RNA interaction using UV melting studies, electrophoretic mobility shift assay, and RNase A footprinting. The results demonstrate that iron(II) supramolecular helicates inhibit Tat-TAR interaction at nanomolar concentrations by binding to TAR RNA. These studies provide a new insight into the biological potential of metallosupramolecular helicates.

No MeSH data available.


Related in: MedlinePlus