4 October 2017:
With only two new antibiotic classes being discovered and developed in the last 50 years, Professor Andrew Abell, CNBP Chief Investigator and his team at the University of Adelaide have been featured on the NHMRC website as one of the ‘ten best’ research stories of the year.
Prof Abell and team are going back to the fundamentals of chemical science in an attempt to develop a new class of antibiotics.
Motivated by a desire to understand the molecular basis of key biological processes, Professor Abell is exploring small molecules that selectively bind to bacterial proteins, as a potential mechanism for limiting bacterial survival.
Read the full story of Prof Abell’s antibiotic focused research here!
6 September 2017:
The first reversible ‘turn-off’ sensor for Glutathione has been reported by CNBP researchers in a paper published in the science journal Biosensors.
The paper is accessible online (open access).
Dr Sabrina Heng notes:
γ-Glutamyl-cysteinyl-glycine (GSH) plays a critical role in maintaining redox homeostasis in biological systems and a decrease in its cellular levels is associated with disease. Many diseases including Parkinson’s, cancer, heart diseases and Alzheimer’s are indicated by a decrease in GSH levels. In this case, a ‘turn on’ sensor would result in reduced fluorescence relative to healthy cells. An important advance would come from the development of a sensor that is measurably turned off by GSH and back on by a lower level of GSH. This would then provide an opportunity to sense reduced GSH levels during the onset of important diseases.
With that in mind we have rationally designed, to the best of our knowledge, the first reversible, reaction-based ‘turn-off’ probe that is suitable for sensing decreasing levels of GSH, a situation known to occur at the onset of various diseases. We have demonstrated that the sensor can be used to detect changes of intracellular GSH in live HEK 293 cells to provide a potentially regenerable sensor for monitoring lower levels of intracellular GSH as associated with the onset of important diseases.
Publication title: A Rationally Designed Reversible ‘Turn-Off’ Sensor for Glutathione.
Authors: Sabrina Heng (pictured), Xiaozhou Zhang, Jinxin Pei and Andrew D. Abell.
Abstract: γ-Glutamyl-cysteinyl-glycine (GSH) plays a critical role in maintaining redox homeostasis in biological systems and a decrease in its cellular levels is associated with diseases. Existing fluorescence-based chemosensors for GSH acts as irreversible reaction-based probes that exhibit a maximum fluorescence (‘turn-on’) once the reaction is complete, regardless of the actual concentration of GSH. A reversible, reaction-based ‘turn-off’ probe (1) is reported here to sense the decreasing levels of GSH, a situation known to occur at the onset of various diseases. The more fluorescent merocyanine (MC) isomer of 1 exists in aqueous solution and this reacts with GSH to induce formation of the ring-closed spiropyran (SP) isomer, with a measurable decrease in absorbance and fluorescence (‘turn-off’). Sensor 1 has good aqueous solubility and shows an excellent selectivity for GSH over other biologically relevant metal ions and aminothiol analytes. The sensor permeates HEK 293 cells and an increase in fluorescence is observed on adding buthionine sulfoximine, an inhibitor of GSH synthesis.
1 September 2017:
Understanding the electronic properties inherent to peptides is crucial for controlling charge transfer, and precursory to the design and fabrication of bio-inspired next generation electronic components.
However, to achieve this objective one must first be able to predict and control the associated charge transfer mechanisms.
Here CNBP researchers demonstrate for the first time a controllable mechanistic transition in peptides resulting directly from the introduction of a side-bridge.
Journal: RSC Advances.
Publication title: A controllable mechanistic transition of charge transfer in helical peptides: from hopping to superexchange.
Authors: Jingxian Yu (pictured), John R. Horsley and Andrew D. Abell.
For more information, access the paper here.
15 June 2017:
Researchers from CNBP (lead author Dr Sabrina Heng pictured), have just had a paper published, reporting on three new spiropyran-based reversible sensors for calcium ion.
Journal: Sensors and Actuators B: Chemical.
Publication title: Photoswitchable calcium sensor: ‘On’–‘Off’ sensing in cells or with microstructured optical fibers.
Authors: Sabrina Heng, Adrian M. Mak, Roman Kostecki, Xiaozhou Zhang, Jinxin Peia, Daniel B. Stubing, Heike Ebendorff-Heidepriema, Andrew D. Abell.
Abstract: Calcium is a ubiquitous intracellular signaling ion that plays a critical role in the modulation of fundamental cellular processes. A detailed study of these processes requires selective and reversible sensing of Ca2+ and an ability to quantify and monitor concentration changes in a biological setting. Three new, rationally designed, synthesized and photoswitchable spiropyran-based reversible sensors for Ca2+ are reported. Sensor 1a is highly selective for Ca2+ with an improved profile relative to the other two analogues, 1b and 1c. Formation of the merocyanine–Ca2+ complex is proportional to an increase in Ca2+ released from HEK293 cells on stimulation with ionomycin. The photophysical processes surrounding the binding of Ca2+ to compound 1a were further explored using computational methods based on density functional theory (DFT). The ability of sensor 1a to bind Ca2+ and photoswitch reversibly was also characterized using silica suspended-core microstructured optical fiber (SCF). These SCF experiments (with 100 nM Ca2+) represent a first step toward developing photoswitchable, minimally invasive and highly sensitive Ca2+ sensing platforms for use in a biological setting.
The paper is accessible online.
15 December 2016:
CNBP researchers were at the forefront of this year’s Biofocus Conference held at Macquarie University, 15 December 2016.
Early career Centre researchers Annemarie Nadort, Lindsay Parker and Nima Sayyadi sat on the conference organising committee, Centre Deputy Director Ewa Goldys (pictured) opened proceedings while CNBP Chief Investigator Prof Andrew Abell (from the University of Adelaide) delivered an extremely well received plenary talk titled, “Defining biomolecular structure and function in solution and on surfaces: new therapeutics and biological probes.”
The annual conference provides a platform for the multidisciplinary community at Macquarie University to present and communicate research, discuss research outcomes and facilitate interdisciplinary collaborations spanning the fields of of biomedical sciences, biomedical engineering, physics, chemistry and medicine.
Feedback from attendees at this year’s event was extremely positive with plenty of formal and informal scientific discussion taking place between sessions.
29 November 2016:
CNBP researchers (lead author Jingxian Yu pictured), have published a paper exploring the quantum interference effects on electronic transport in peptides. The work has just been reported in the journal ‘Molecular Systems Design & Engineering’ and is accessible online.
Journal: Molecular Systems Design & Engineering.
Title: Exploiting the interplay of quantum interference and backbone rigidity on electronic transport in peptides: A step towards bio-inspired quantum interferometers.
Authors: Jingxian Yu, John R Horsley and Andrew D Abell.
Abstract: Electron transfer in peptides provides an opportunity to mimic nature for applications in bio-inspired molecular electronics. However, quantum interference effects, which become significant at the molecular level, have yet to be addressed in this context. Electrochemical and theoretical studies are reported on a series of cyclic and linear peptides of both β-strand and helical conformation, to address this shortfall and further realize the potential of peptides in molecular electronics. The introduction of a side-bridge into the peptides provides both additional rigidity to the backbone, and an alternative pathway for electron transport. Electronic transport studies reveal an interplay between quantum interference and vibrational fluctuations. We utilize these findings to demonstrate two distinctive peptide-based quantum interferometers, one exploiting the tunable effects of quantum interference (β-strand) and the other regulating the interplay between the two phenomena (310-helix).
10 November 2016:
In this latest review paper, CNBP researchers Xiaozhou (Michelle) Zhang (pictured left) and Prof Andrew Abell explore the preparation and properties of peptide-based macrocycles that target important therapeutic aims for conditions such as cancer, cataract, HIV, and neurological diseases.
Journal: Australian Journal of Chemistry.
Title: Macrocyclic Peptidomimetics Prepared by Ring-Closing Metathesis and Azide-Alkyne Cycloaddition.
Authors: Ashok D Pehere, Xiaozhou Zyhang and Andrew D Abell.
Abstract: Macrocycles are finding increasing use as a means to define the backbone geometries of peptides and peptidomimetics.Ring-closing metathesis and CuI-catalyzed azide–alkyne cycloaddition are particularly useful for introducing such rings and they do so in high yield and with a good functional group tolerance and compatibility. Here, we present an overview of the use of these two methods, with reference to selected examples and particular reference to b-strand peptidomimetics for use as protease inhibitors.
The paper is accessible online.
13 September 2016:
CNBP researchers Xiaozhou (Michelle) Zhang & Prof Andrew Abell explore peptidomimetic boronates as proteasome inhibitors in the latest issue of ACS Medicinal Chemistry Letters.
Journal: ACS Medicinal Chemistry Letters.
Title: New Peptidomimetic Boronates for Selective Inhibition of the Chymotrypsin-Like Activity of the 26S Proteasome.
Authors: Xiaozhou Zhang, Alaknanda Adwal, Andrew G Turner, David F Callen and Andrew D Abell.
Abstract: Proteasome is a large proteinase complex that degrades proteins via its three catalytic activities. Among these activities, the ‘chymotrypsin-like’ activity has emerged as the focus of drug discovery in cancer therapy. Here, we report new peptidomimetic boronates that are highly specific for the chymotrypsin-like catalytic activity of the proteasome. These new specific proteasome inhibitors demonstrated higher in vitro potency and selective cytotoxicity for cancer cells compared to benchmark proteasome inhibitors, bortezomib and carfilzomib. In breast cancer cell lines, treatment with 1a or
2a induced accumulation of the high molecular weight polyubiqutinated proteins at similar levels observed for borte-zomib and carfilzomib, indicating that cancer cell death caused by 1a/2a is chiefly due to proteasome inhibition.
The paper can be accessed online.
24 August 2016:
There have been a number of updates from CNBP’s Recognise Theme (focused on creating optically-controlled surfaces to recognise molecules in living systems) led by Chief Investigator Prof Andrew Abell (pictured top left) from the University of Adelaide. Updates include –
- Prof Irene Hudson from the University of Newcastle has been appointed Associative Investigator, as has Dr Abel Santos from the School of Chemical Engineering, University of Adelaide. Both will work closley with the recognise theme
- Birgit Gaiser will be joining the recognise theme for 6 months from the University of Copenhagen as an international visitor
- Kathryn Palasis has joined the recognise theme as an honours student to work on photoswitchable proteasome inhibitors
- Aniket Kulkarni has joined the recognise theme as a new PhD student to work on hypoxia switchable anti cancer agents
- Two new postdocs join the recognise theme: Dr Beatriz Blanco Rodriguez has joined to work on hypoxia switchable anti cancer agents (funded from outside the CNBP). Dr Borja Lopez Perez has also joined the recognise theme to work on hypoxia switchable anti cancer agents (and likewise is funded from outside the CNBP)
- Yuan Qi Yeoh from the recognise theme was awarded first class honours
- And finally, Pan Yanbo from Hong Kong has been awarded a University of Adelaide international PhD scholarship to join the recognise theme.
Busy and exciting times!
10 August 2016:
Researchers from the CNBP have published a paper representing the first major study of the stability and compatibility of the major classes of photochromic compounds within the microstructured optical fibre (MOF) environment.
In developing light-responsive surfaces, investigators face several challenges, not only in achieving high photostationary states and fully reversible switching, but also in fluorescence properties and fatigue resistance upon continuous exposure to high intensity light. However, information on the latter two are often lacking as studies on photochromic compounds are often focused on photoswitching, or absorbance and colour changes. To address this gap in literature, the fluorescence and photostability of four major types of photochromic molecules (azobenzene, spiropyran, indolyfulgide and diarylalkene) when dissolved in DMSO, or acetonitrile, or adsorbed to a MOF silica surface were investigated.
Journal: Sensors and Actuators B: Chemical.
Publication title: A Comparative Study of the Fluorescence and Photostability of Common Photoswitches in Microstructured Optical Fibre.
Authors: Daniel B. Stubing (pictured top left), Sabrina Heng, Tanya M. Monro and Andrew D. Abell.
Abstract: The fluorescence spectra and photostability under 532 nm laser excitation of four different common photoswitches (an azobenzene, spiropyran, indolylfulgide, and a diarylperfluorocyclopentene) were investigated in a silica microstructured optical fibre. An example of each photoswitch was examined in solution and physically adsorbed to the silica fibre surface. This comparison was made to define fluorescence behaviour in these two states and to determine which photoswitch has the best performance in this light intense microenvironment. The azobenzene and the spiropyran switches demonstrated the strongest fluorescence response and the least degradation of the fluorescence signal.
The paper is available online.