Characterization of Aptamer BC 007 Substance and Product Using Circular Dichroism and Nuclear Magnetic Resonance Spectroscopy

Weißhoff, Hardy; Wenzel, Katrin; Schulze-Rothe, Sarah; Nikolenko, Heike; Davideit, Hanna; Becker, Niels-Peter; Göttel, Peter; Srivatsa, G. Susan; Dathe, Margitta; Müller, Johannes; Haberland, Annekathrin

doi:10.1016/j.xphs.2018.04.003

Cited by 3 publications

(5 citation statements)

References 25 publications

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“…In particular, the H6 protons of the nucleotides T13 and T4, which belong to the TT loop of the folded BC 007, showed strong line broadening. The assignment of the BC 007 signals in both BC 007-peptide mixtures succeeded analogously to the assignment of the signals in the BC 007-potassium sample, and largely corresponded to the 1 H-signal assignments known from the literature [ 32 , 33 ].…”

Section: Resultssupporting

confidence: 67%

“…From previous investigations with this aptamer, which was originally selected as a potential short-lasting thrombin inhibitor for transient anticoagulation during coronary bypass graft surgery [ 28 ] yet failed in this indication because of a lack of a persistent effect, resulting in a suboptimal dosing profile (too high a dose for a therapeutic effect), we learned that sections of the protein binding sequence (RTRYERNIE (from PDB ID entry: 1HAO, source [ 29 ] from the exosite 1) are already sufficient to enforce binding (data not shown). In this very special case, the formation of the quadruple structure of the aptamer is a very convenient readout of specific intermolecular interactions that can be easily detected via NMR spectroscopy [ 30 ] and CD-spectroscopy [ 31 , 32 ]. In aqueous solution, BC 007 presents in a random coil structure.…”

Section: Resultsmentioning

confidence: 99%

“…

Figure 1 NMR spectroscopic evaluation of the molecular interaction of BC 007 with sequence sections of the spike protein and the RNA dependent RNA polymerase of SARS-CoV-2. A: The upper NMR spectrum of BC 007 (1 mM) in combination with 0.9 mM YRLFRK (in blue colour) shows formation of the quadruplex structure of BC 007 induced by molecular interaction with the peptide which is clearly recognisable by eight imino signals between 11.5 and 12.5 ppm which are comparable to the well-known potassium-induced fold of BC 007 [ 32 ] (lower green spectrum). Substances were dissolved in 0.5 ml pure H 2 O/D 2 O mixture without any additives.…”

Section: Resultsmentioning

confidence: 99%

“…Since BC 007 also folds in the presence of Na + ions – although a lot less compared to K + [ 32 ] – the contribution of sodium ions to folding was controlled in this way and was about 20% (also compare to the 26.5% caused by NRKRISN). Even in 154 mM Na + , the folding capacity only reaches about 30% of the maximal folding effect [ 32 ]. Therefore, sodium did not have any essential influence on the CD-spectroscopic BC 007-peptide binding evaluation.…”

Section: Resultsmentioning

confidence: 99%

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Aptamer BC 007 - Efficient binder of spreading-crucial SARS-CoV-2 proteins

Weißhoff¹,

Krylova²,

Nikolenko³

et al. 2020

Heliyon

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Corona virus disease 2019 (COVID-19) is a respiratory disease caused by a new coronavirus (SARS-CoV-2) which causes significant morbidity and mortality. The emergence of this novel and highly pathogenic SARS-CoV-2 and its rapid international spread poses a serious global public health emergency. To date 32,174,627 cases, of which 962,613 (2.99%) have died, have been reported ( https://www.who.int/westernpacific/health-topics/coronavirus , accessed 23 Sep 2020). The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. There are still not many SARS-CoV-2-specific and effective treatments or vaccines available. A second round of infection is obviously unavoidable. Aptamers had already been at the centre of interest in the fight against viruses before now. The selection and development of a new aptamer is, however, a time-consuming process. We therefore checked whether a clinically developed aptamer, BC 007, which is currently in phase 2 of clinical testing for a different indication, would also be able to efficiently bind DNA-susceptible peptide structures from SARS-CoV-2-spreading crucial proteins, such as the receptor binding domain (RBD) of the spike protein and the RNA dependent RNA polymerase of SARS-CoV-2 (re-purposing). Indeed, several such sequence-sections have been identified. In particular for two of these sequences, BC 007 showed specific binding in a therapy-relevant concentration range, as shown in Nuclear magnetic resonance (NMR)- and Circular dicroism (CD)-spectroscopy and isothermal titration calorimetry (ITC). The excellent clinical toxicity and tolerability profile of this substance opens up an opportunity for rapid clinical testing of its COVID-19 effectiveness.

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Section: Resultssupporting

confidence: 67%

Section: Resultsmentioning

confidence: 99%

“…

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Aptamer BC 007 - Efficient binder of spreading-crucial SARS-CoV-2 proteins

Weißhoff¹,

Krylova²,

Nikolenko³

et al. 2020

Heliyon

Self Cite

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“…In addition to its use in exploring the secondary structure, CD is also a valuable tool for revealing the structural changes of aptamers upon binding with ligands [67]. However, the CD spectrum represents only global features of molecules; it cannot provide deep speculation into the binding pocket, which needs to be interpreted with other means, such as computational structure prediction, nuclear magnetic resonance (NMR) or X-ray diffraction, to gain more detailed structural information of the aptamer-ligand complex [66,68,69].…”

Section: Essential Characterization Of Pesticide Aptamersmentioning

confidence: 99%

Pesticide Aptasensors—State of the Art and Perspectives

Phopin

Tantimongcolwat

2020

Sensors

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Contamination by pesticides in the food chain and the environment is a worldwide problem that needs to be actively monitored to ensure safety. Unfortunately, standard pesticide analysis based on mass spectrometry takes a lot of time, money and effort. Thus, simple, reliable, cost-effective and field applicable methods for pesticide detection have been actively developed. One of the most promising technologies is an aptamer-based biosensor or so-called aptasensor. It utilizes aptamers, short single-stranded DNAs or RNAs, as pesticide recognition elements to integrate with various innovative biosensing technologies for specific and sensitive detection of pesticide residues. Several platforms for aptasensors have been dynamically established, such as colorimetry, fluorometry, electrochemistry, electrochemiluminescence (ECL) and so forth. Each platform has both advantages and disadvantages depending on the purpose of use and readiness of technology. For example, colorimetric-based aptasensors are more affordable than others because of the simplicity of fabrication and resource requirements. Electrochemical-based aptasensors have mainly shown better sensitivity than others with exceedingly low detection limits. This paper critically reviews the progression of pesticide aptasensors throughout the development process, including the selection, characterization and modification of aptamers, the conceptual frameworks of integrating aptamers and biosensors, the ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free and deliverable to end users) criteria of different platforms and the future outlook.

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Research advances of DNA aptasensors for foodborne pathogen detection

Chen

Wang

et al. 2019

Critical Reviews in Food Science and Nutrition

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Characterization of Aptamer BC 007 Substance and Product Using Circular Dichroism and Nuclear Magnetic Resonance Spectroscopy

Cited by 3 publications

References 25 publications

Aptamer BC 007 - Efficient binder of spreading-crucial SARS-CoV-2 proteins

Aptamer BC 007 - Efficient binder of spreading-crucial SARS-CoV-2 proteins

Pesticide Aptasensors—State of the Art and Perspectives

Research advances of DNA aptasensors for foodborne pathogen detection

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