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Exploring the role of the α-carboxyphosphonate moiety in the HIV-RT activity of α-carboxy nucleoside phosphonates

Overview of attention for article published in Organic and Biomolecular Chemistry, January 2016
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Title
Exploring the role of the α-carboxyphosphonate moiety in the HIV-RT activity of α-carboxy nucleoside phosphonates
Published in
Organic and Biomolecular Chemistry, January 2016
DOI 10.1039/c5ob02507a
Pubmed ID
Authors

Nicholas D. Mullins, Nuala M. Maguire, Alan Ford, Kalyan Das, Eddy Arnold, Jan Balzarini, Anita R. Maguire

Abstract

As α-carboxy nucleoside phosphonates (α-CNPs) have demonstrated a novel mode of action of HIV-1 reverse transcriptase inhibition, structurally related derivatives were synthesized, namely the malonate , the unsaturated and saturated bisphosphonates and , respectively and the amide . These compounds were evaluated for inhibition of HIV-1 reverse transcriptase in cell-free assays. The importance of the α-carboxy phosphonoacetic acid moiety for achieving reverse transcriptase inhibition, without the need for prior phosphorylation, was confirmed. The malonate derivative was less active by two orders of magnitude than the original α-CNPs, while displaying the same pattern of kinetic behavior; interestingly the activity resides in the "L"-enantiomer of , as seen with the earlier series of α-CNPs. A crystal structure with an RT/DNA complex at 2.95 Å resolution revealed the binding of the "L"-enantiomer of , at the polymerase active site with a weaker metal ion chelation environment compared to (T-α-CNP) which may explain the lower inhibitory activity of .

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Russia 1 6%
Unknown 15 94%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 4 25%
Researcher 4 25%
Professor 2 13%
Student > Ph. D. Student 1 6%
Other 1 6%
Other 2 13%
Unknown 2 13%
Readers by discipline Count As %
Chemistry 8 50%
Medicine and Dentistry 3 19%
Agricultural and Biological Sciences 1 6%
Unknown 4 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 January 2016.
All research outputs
#20,970,494
of 25,756,911 outputs
Outputs from Organic and Biomolecular Chemistry
#5,636
of 6,872 outputs
Outputs of similar age
#297,478
of 401,844 outputs
Outputs of similar age from Organic and Biomolecular Chemistry
#331
of 436 outputs
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So far Altmetric has tracked 6,872 research outputs from this source. They receive a mean Attention Score of 3.7. This one is in the 7th percentile – i.e., 7% of its peers scored the same or lower than it.
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