Approach to a synthetic esterase

Project A: The development of a supported sixteen residue peptidyl model incorporating the 'reactive triad' serine, histidine and aspartic acid, found within serine protease enzymes. The methodology was designed to allow rapid screening of a combinatorial library of simple peptides containing the reactive triad, some of which were anticipated to show synthetic esterase activity. It is envisaged that this could be undertaken be observing selective cleavage of a highly coloured red azo dye tethered through the ester under investigation to the peptide via a glycol linker. One peptidyl system has been synthesised and investigated to allow the development of the methodology and it was found that intramolecular hydrolysis could be observed when glycol linkers of optimal length were utilised under favourable conditions. Project B: Vancomycin was modified with extended glycol chains containing a terminal double bond to allow covalent dimerisation via cross coupling metathesis. Binding of the vancomycin monomers and dimers to an N-acetyl-L-Lys-D-Ala-D-Ser peptide model has been demonstrated via electrospray ionisation mass spectrometry by Professor Albert Heck at Utrecht, Holland and in-vivo studies are ongoing to elucidate if enhanced vancomycin activity towards vancomycin resistant bacteria can be observed

Destabilization of α-helical structure in solution improves bactericidal activity of antimicrobial peptides: Opposing effects on bacterial and viral targets

We have previously examined the mechanism of antimicrobial peptides on the outer membrane of vaccinia virus. Here we show that the formulation of peptides LL37 and magainin-2B amide in polysorbate 20 (Tween-20™) results in greater reductions in virus titre than formulation without detergent, and the effect is replicated by substitution of polysorbate 20 with high ionic strength buffer. In contrast, formulation with polysorbate 20 or high ionic strength buffer has the opposite effect on bactericidal activity of both peptides, resulting in lesser reductions in titre for both gram-positive and gram-negative bacteria. Circular dichroism spectroscopy shows that the differential action of polysorbate 20 and salt on the virucidal and bactericidal activities correlates with the α-helical content of peptide secondary structure in solution, suggesting that the virucidal and bactericidal activities are mediated through distinct mechanisms. The correlation of a defined structural feature with differential activity against a host-derived viral membrane and the membranes of both gram-positive and gram-negative bacteria suggests that overall helical content in solution under physiological conditions is an important feature for consideration in the design and development of candidate peptide-based antimicrobial compounds

Natural history of falls in an incident cohort of Parkinson’s disease: early evolution, risk and protective features

The natural history of falls in early Parkinson’s disease (PD) is poorly understood despite the profound effect of falls on outcome. The primary aim of this study was to describe the natural history of falls, and characterise fallers over 54 months in 99 newly diagnosed people with PD. Seventy-nine (79.7%) participants fell over 54 months and 20 (20.3%) remained falls-naïve. Twenty six (26.2%) reported retrospective falls at baseline. Gait outcomes, disease severity and self-efficacy significantly discriminated across groups. Subjective cognitive complaints emerged as the only significant cognitive predictor. Without exception, outcomes were better for non-fallers compared with fallers at any time point. Between group differences for 54 month fallers and non-fallers were influenced by the inclusion of retrospective fallers and showed a broader range of discriminant characteristics, notably stance time variability and balance self-efficacy. Single fallers (n = 7) were significantly younger than recurrent fallers (n = 58) by almost 15 years (P = 0.013). Baseline performance in early PD discriminates fallers over 54 months, thereby identifying those at risk of falls. Clinical profiles for established and emergent fallers are to some extent distinct. These results reiterate the need for timely interventions to improve postural control and gait

Instantaneous Capture and Mineralization of Flue Gas Carbon Dioxide: Pilot Scale Study

Multiple CO2 capture and storage (CCS) processes are required to address anthropogenic CO2 problems. However, a method which can directly capture and mineralize CO2 at a point source, under actual field conditions, has advantages and could help offset the cost associated with the conventional CCS technologies. The mineral carbonation (MC), a process of converting CO2 into stable minerals (mineralization), has been studied extensively to store CO2. However, most of the MC studies have been largely investigated at laboratory scale. Objectives of this research were to develop a pilot scale AMC (accelerated mineral carbonation) process and test the effects of flue gas moisture content on carbonation of fly ash particles. A pilot scale AMC process consisting of a moisture reducing drum (MRD), a heater/humidifier, and a fluidized-bed reactor (FBR) was developed and tested by reacting flue gas with fly ash particles at one of the largest coal-fired power plants (2120 MW) in the USA. The experiments were conducted over a period of 2 hr at ~ 300 SCFM flow-rates, at a controlled pressure (115.1 kPa), and under different flue gas moisture contents (2-16%). The flue gas CO2 and SO2 concentrations were monitored before and during the experiments by an industrial grade gas analyzer. Fly ash samples were collected from the reactor sample port from 0-120 minutes and analyzed for total inorganic carbon (C), sulfur (S), and mercury (Hg). From C, S, and Hg concentrations, %calcium carbonate (CaCO3), %sulfate (SO42-), and %mercury carbonate (HgCO3) were calculated, respectively. Results suggested significant mineralization of flue gas CO2, SO2, and Hg within 10-15 minutes of reaction. Among different moisture conditions, ~16% showed highest conversion of flue gas CO2 and SO2 to %CaCO3 and %SO42- in fly ash samples. For example, an increase of almost 4% in CaCO3 content of fly ash was observed. Overall, the AMC process is cost-effective with minimum carbon footprint and can be retrofitted to coal fired power plants (existing and/or new) as a post-combustion unit to minimize flue gas CO2, SO2, and Hg emissions into the atmosphere. Used in conjunction with capture and geologic sequestration, the AMC process has the potential to reduce overall cost associated with CO2 separation/compression/transportation/pore space/brine water treatment. It could also help protect sensitive amines and carbon filters used in flue gas CO2 capture and separation process and extend their life