Real-time monitoring of disintegration activity of catalytic core domain of HIV-1 integrase using molecular beacon

Zhang, Dawei; Zhao, Mingming; He, Hong; Guo, Shun‐Xing

doi:10.1016/j.ab.2013.05.032

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…One of such examples is the present pandemic of human immunodeficiency virus (HIV/AIDS), which originated in west-central Africa during the early twentieth century, and has caused nearly 30 million deaths since the first case of AIDS was reported on June 5, 1981 (De Cock et al, 2011). At present, the majority of the developed methods for HIV detection are based on the detection of the presence of antibodies that the patient’s body makes against HIV (Bhimji et al, 2013; Laird et al, 2013), direct molecular recognition of HIV and its components such as specific nucleic acid sequences or antigens (Zhang et al, 2013; Palmer et al, 2003; Yan et al, 2011), or measurement of the activity of HIV-1 protease (HIV-1 PR) (Esseghaier et al, 2013; Biswas et al, 2011; Davis et al, 2009), many of which are often laborious and time-consuming, and/or require the use of labels or sophisticated instruments.…”

Section: Introductionmentioning

confidence: 99%

Real-time label-free measurement of HIV-1 protease activity by nanopore analysis

Wang

Yang

Zhou

et al. 2014

Biosensors and Bioelectronics

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A label-free method for the measurement of the activity of HIV-1 protease is developed by real-time monitoring of the cleavage of a peptide substrate by HIV-1 protease in a nanopore. The method is rapid and sensitive: picomolar concentrations of HIV-1 protease could be detected in ~10 minutes. Simulated clinical samples are analyzed, and the activity of HIV-1 protease could be accurately detected. Our developed nanopore sensor design strategy should find useful application in the development of stochastic sensors for other proteases of medical, pharmaceutical, and biological importance.

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Section: Introductionmentioning

confidence: 99%

Real-time label-free measurement of HIV-1 protease activity by nanopore analysis

Wang

Yang

Zhou

et al. 2014

Biosensors and Bioelectronics

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“…Finally, disintegration can be considered to be the reverse of the ST reaction. However, this reaction was only observed in vitro and can be performed by IN lacking the N-terminal or the C-terminal domain, in contrast to the three above-mentioned activities (Gerton and Brown, 1997; Leh et al, 2000; Zhang et al, 2013). …”

Section: Integrase and Its Catalytic Activitiesmentioning

confidence: 99%

Different Pathways Leading to Integrase Inhibitors Resistance

2017

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Integrase strand-transfer inhibitors (INSTIs), such as raltegravir (RAL), elvitegravir, or dolutegravir (DTG), are efficient antiretroviral agents used in HIV treatment in order to inhibit retroviral integration. By contrast to RAL treatments leading to well-identified mutation resistance pathways at the integrase level, recent clinical studies report several cases of patients failing DTG treatment without clearly identified resistance mutation in the integrase gene raising questions for the mechanism behind the resistance. These compounds, by impairing the integration of HIV-1 viral DNA into the host DNA, lead to an accumulation of unintegrated circular viral DNA forms. This viral DNA could be at the origin of the INSTI resistance by two different ways. The first one, sustained by a recent report, involves 2-long terminal repeat circles integration and the second one involves expression of accumulated unintegrated viral DNA leading to a basal production of viral particles maintaining the viral information.

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“…The monitoring of enzyme activity with molecular beacons has aided the development of new drugs and enabled elucidation of the mechanisms of catalytic processes, e.g. the real time monitoring of HIV-1 integrase has made it possible to observe disintegration of the catalytic core domain of the virus (Zhang et al, 2013a). These important applications of MBs are discussed in the next sections.…”

Section: Enzyme Detection Using Molecular Beaconsmentioning

confidence: 99%

Biosensors based on molecular beacons

Stobiecka

Chałupa²

2015

Chemical Papers

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A fundamental molecular beacon (MB) consists of a special short nucleic acid strand with a fluorophore-quencher pair attached to its ends. It provides a unique framework that is susceptible to conformational transitions between a hairpin (closed) conformation and an extended (open) conformation. These two conformations are readily discernible because of their differing fluorescence emission characteristics. The broad applicability of the robust MB sensing platform has attracted widespread interest, resulting in extensive research studies ranging from theoretical and bioanalytical chemistry to molecular biology and biomedical applications. In this paper, the principles of MB design and the modes and mechanisms of MB operation are reviewed, including MB modifications based on the utilisation of a thymidine-thymidine mismatch in hybridised MB stem, aptamers, peptides and locked nucleic acid strands in an MB loop, as well as plasmonic quenchers, quantum dots and interactions with graphene and graphene oxide. Specific applications of MBs in the analysis of enzymes, DNA mutation, phosphorylation, methylation and ligation, followed by the detection of pathogens and applications in cancer and other disease diagnostics and therapeutics are also reviewed. Molecular beacon-based sensing platforms are expanding rapidly and offer a promising bioanalytical tool for inexpensive and reliable analysis for research and field diagnostics.

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Real-time monitoring of disintegration activity of catalytic core domain of HIV-1 integrase using molecular beacon

Cited by 5 publications

References 21 publications

Real-time label-free measurement of HIV-1 protease activity by nanopore analysis

Real-time label-free measurement of HIV-1 protease activity by nanopore analysis

Different Pathways Leading to Integrase Inhibitors Resistance

Biosensors based on molecular beacons

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