Targeting Intrinsically Disordered Transcription Factors: Changing the Paradigm.

Increased understanding of intrinsically disordered proteins (IDPs) and protein regions has revolutionized our view of the relationship between protein structure and function. Data now support that IDPs can be functional in the absence of a single, fixed, three-dimensional structure. Due to their dynamic morphology, IDPs have the ability to display a range of kinetics and affinity depending on what the system requires, as well as the potential for large-scale association. Although several studies have shed light on the functional properties of IDPs, the class of intrinsically disordered transcription factors (TFs) is still poorly characterized biophysically due to their combination of ordered and disordered sequences. In addition, TF modulation by small molecules has long been considered a difficult or even impossible task, limiting functional probe development. However, with evolving technology, it is becoming possible to characterize TF structure-function relationships in unprecedented detail and explore avenues not available or not considered in the past. Here we provide an introduction to the biophysical properties of intrinsically disordered TFs and we discuss recent computational and experimental efforts toward understanding the role of intrinsically disordered TFs in biology and disease. We describe a series of successful TF targeting strategies that have overcome the perception of the "undruggability" of TFs, providing new leads on drug development methodologies. Lastly, we discuss future challenges and opportunities to enhance our understanding of the structure-function relationship of intrinsically disordered TFs.

Surface modification of graphene nanopores for protein translocation.

Studies of DNA translocation through graphene nanopores have revealed their potential for DNA sequencing. Here we report a study of protein translocation through chemically modified graphene nanopores. A transmission electron microscope (TEM) was used to cut nanopores with diameters between 5 and 20 nm in multilayer graphene prepared by chemical vapor deposition (CVD). After oxygen plasma treatment, the dependence of the measured ionic current on salt concentration and pH was consistent with a small surface charge induced by the formation of carboxyl groups. While translocation of gold nanoparticles (10 nm) was readily detected through such treated pores of a larger diameter, translocation of the protein ferritin was not observed either for oxygen plasma treated pores, or for pores modified with mercaptohexadecanoic acid. Ferritin translocation events were reliably observed after the pores were modified with the phospholipid-PEG (DPPE-PEG750) amphiphile. The ion current signature of translocation events was complex, suggesting that a series of interactions between the protein and pores occurs during the process.

Mass transport through vertically aligned large diameter MWCNTs embedded in parylene.

We have fabricated porous membranes using a parylene encapsulated vertically aligned forest of multi-walled carbon nanotubes (MWCNTs, about 7 nm inner diameter). The transport of charged particles in electrolyte through these membranes was studied by applying electric field and pressure. Under an electric field in the range of 4.4 × 10(4) V m(-1), electrophoresis instead of electroomosis is found to be the main mechanism for ion transport. Small molecules and 5 nm gold nanoparticles can be driven through the membranes by an electric field. However, small biomolecules, like DNA oligomers, cannot. Due to the weak electric driving force, the interactions between charged particles and the hydrophobic CNT inner surface play important roles in the transport, leading to enhanced selectivity for small molecules. Simple chemical modification on the CNT ends also induces an obvious effect on the translocation of single strand DNA oligomers and gold nanoparticles under a modest pressure (<294 Pa).

Assessment of air pollution tolerance index of some trees in Moradabad city, India.

To see the relative tolerance of the plant species, ten different plant species i.e. Ficus rumphii, Pongamia pinnata, Alstonia scholaris, Holoptelea integrifolia, Saraca indica, Pithecolobium dulcis, Cassia simea, Bauhinia variegata, Azadirachta indica and Grewelia robusta was taken from residential (SI), industrial (SII) and commercial (SIII) area of the city as this florais very much common to the Brass city and is planted on the roadside. The quality of air with respect to SPM, SO2 and NO2 has been also assessed on respective sites to see its effect on biochemical parameters of the leaves i.e. pH, total water content, chlorophyll and ascorbic acid and evaluate the (air pollution tolerance index (APTI) of various plants. It was concluded that Pongamia pinnata 15.8, Pithecolobium dulcis 34.8, Holoptelea integrifolia 55.8 and Saraca indica 52.0 have very high APTI value over control so these are considered as high tolerant tree species, Ficus rumphii 35.7, Azadirachta indica 30.5 and Grewelia robusta 34.3 have slightlymoreAPTI value over control so these are considered as moderately tolerant tree species and Alstonia scholaris 21.5, Cassia simea 6.09 and Bauhinia variegata 18.22 have lessAPTI value than control, so these are sensitive species respectively. One way ANOVA finds the obtained values to be highly significant (p < 0.001) at the industrial site. Thus present findings show that Brass and allied industries are the prominent sources responsible for the elevated level of air pollutants at the industrial site.