Reductive power of the archaea right-handed coiled coil nanotube (RHCC-NT) and incorporation of mercury clusters inside protein cages

et al. 2019

Sci Rep

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Polycyclic aromatic hydrocarbons (PAHs) are toxic, mutagenic and among the most damaging chemical compounds with regard to living organisms. Because of their persistence and wide distribution removal from the environment is an important challenge. Here we report a new Nano container matrix based on the deep sea archaea-derived RHCC-Nanotube (RHCC-NT), which rapidly and preferentially binds low molecular weight PAHs. Under controlled-laboratory conditions and using fluorescence spectroscopy in combination with X-ray crystallography and MD simulations, we quantified the real-time binding of low molecular weight PAHs (2–4 rings) to our substrate. Binding coefficients ranged from 5.4 ± 1.6 (fluorene) to 32 ± 7.0 μM (acenaphthylene) and a binding capacity of 85 pmoles PAH per mg RHCC-NT, or 2.12 μmoles in a standard 25 mg sampler. The uptake rate of pyrene was calculated to be 1.59 nmol/hr∙mol RHCC-NT (at 10 C). Our results clearly show that RHCC-NT is uniquely suited as a monitoring matrix for low molecular weight PAHs.

Section: Discussionmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Proteinaceous Nano container Encapsulate Polycyclic Aromatic Hydrocarbons

McDougall

Francisco

et al. 2019

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“…RHCC-NT was first described as an S-layer protein component of the archaea Staphylothermus marinus 13 . It has been shown to possess highly unusual properties in respect to cargo uptake 14 – 17 , targeted drug delivery 18 – 20 and robustness 13 , 21 . Our study focuses on an integrated approach combining structural biology, biophysical and in vitro functional assays to characterize RHCC-NT on physicochemical and biological levels as a unique drug delivery system for targeted 10 B delivery.…”

Section: Introductionmentioning

confidence: 99%

Boron rich nanotube drug carrier system is suited for boron neutron capture therapy

Heide

McDougall

et al. 2021

Sci Rep

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Boron neutron capture therapy (BNCT) is a two-step therapeutic process that utilizes Boron-10 in combination with low energy neutrons to effectively eliminate targeted cells. This therapy is primarily used for difficult to treat head and neck carcinomas; recent advances have expanded this method to cover a broader range of carcinomas. However, it still remains an unconventional therapy where one of the barriers for widespread adoption is the adequate delivery of Boron-10 to target cells. In an effort to address this issue, we examined a unique nanoparticle drug delivery system based on a highly stable and modular proteinaceous nanotube. Initially, we confirmed and structurally analyzed ortho-carborane binding into the cavities of the nanotube. The high ratio of Boron to proteinaceous mass and excellent thermal stability suggest the nanotube system as a suitable candidate for drug delivery into cancer cells. The full physicochemical characterization of the nanotube then allowed for further mechanistic molecular dynamic studies of the ortho-carborane uptake and calculations of corresponding energy profiles. Visualization of the binding event highlighted the protein dynamics and the importance of the interhelical channel formation to allow movement of the boron cluster into the nanotube. Additionally, cell assays showed that the nanotube can penetrate outer membranes of cancer cells followed by localization around the cells’ nuclei. This work uses an integrative approach combining experimental data from structural, molecular dynamics simulations and biological experiments to thoroughly present an alternative drug delivery device for BNCT which offers additional benefits over current delivery methods.

“…X-ray diffraction measurements [5] performed on a polypeptide chain fragment of tetrabrachion show that the stalk is a tetrameric right-handed coiled-coil

composed of four strands oriented in parallel in a right-handed fashion, forming a nanotube with a central channel and four large non-polar cavities which contain water clusters in the native conformation. The

has been shown [5] to be stable at high salt concentrations, temperatures of over 100 ˚C, high pressures and extreme ranges of pH, and several studies have demonstrated that the hydrophobic cavities are able to uptake and store water clusters [5] , elemental sulfur

crowns [8] , [9] , atomic metals clusters [10] , and polycyclic hydrocarbons [11] .…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulations of ortho-carborane nano-diamond storage within the nonpolar channel cavities of a right-handed coiled-coil tetrabrachion nanotube

Computational and Structural Biotechnology Journal

Heide

Roshko

et al. 2021

Graphical abstract Molecular dynamics simulations have been performed on a complex in which clusters of boron in the form of molecules of the nanodiamond ortho-carborane have been inserted into the four large nonpolar cavities of a nanotube of the right-handed coiled-coil RHCC. The techniques of multi-configurational thermodynamic integration, steered molecular dynamics and umbrella sampling have been combined to investigate the energetics of storage of ortho-carborane in the cavities and to map out the free energy landscape of the complex along the central channel and along directions transverse to the central channel. The purpose of the study was to explore potential pathways for the diffusion of ortho-carborane between the cavities and the solvent and to assess the stability of the complex as a possible drug delivery system for boron neutron capture therapy (BNCT). The investigation reveals a complex free energy landscape with a multitude of peaks and valleys, all of which can be related to specific architectural elements of the , and the activation barriers for ortho-carborane capture and release support the requirements for rapid cargo uptake coupled with tight binding to the cavities.