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.
23 June 2016:
CNBP researchers Xiaozhou (Michelle) Zhang (pictured left) and Prof Andrew Abell (CNBP Chief Investigator) report on an NMR and X-ray crystallography-based characterisation of the mechanism by which a new class of macrocyclic peptidomimetic aldehyde inhibits α-chymotrypsin.
This provides molecular level insight into the mechanism and functionalities of proteases, which are crucial for many biological systems including neuronal, embryonic and cardiovascular systems.
Journal: Organic & Biomolecular Chemistry
Publication title: A mechanistic study on the inhibition of α-chymotrypsin by a macrocyclic peptidomimetic aldehyde.
Authors: X. Zhang, J. B. Bruning, J. H. George and A. D. Abell
Abstract: Here we describe an NMR and X-ray crystallography-based characterisation of the mechanism by which a new class of macrocyclic peptidomimetic aldehyde inhibits α-chymotrypsin. In particular, a 13C-labelled analogue of the inhibitor was prepared and used in NMR experiments to confirm formation of a hemiacetal intermediate on binding with α-chymotrypsin. Analysis of an X-ray crystallographic structure in complex with α-chymotrypsin reveals that the backbone adopts a stable β-strand conformation as per its design. Binding is further stabilised by interaction with the oxyanion hole near the S1 subsite and multiple hydrogen bonds.
The paper is accessible online.
13 May 2016:
CNBP researchers have created nanoscale biosensors that are capable of sensing Zn2+ ions in biological samples. Such sensors have potential application in disease diagnosis and study, as well as in environmental sensing. The study was published in the journal ACS Applied Materials and Interfaces, May 13th, 2016.
Publication title: Microstructured Optical Fiber-based Biosensors: Reversible and Nanoliter-Scale Measurement of Zinc Ions.
Authors: Sabrina Heng (pictured), Christopher A. McDevitt, Roman Kostecki, Jacqueline R. Morey, Bart A. Eijkelkamp, Heike Ebendorff-Heidepriem, Tanya M. Monro, and Andrew D. Abell.
Sensing platforms that allow rapid and efficient detection of metal ions would have applications in disease diagnosis and study, as well as environmental sensing. Here, we report the first microstructured optical fiber-based biosensor for the reversible and nanoliter-scale measurement of metal ions. Specifically, a photoswitchable spiropyran Zn2+ sensor is incorporated within the microenvironment of a liposome attached to microstructured optical fibers (exposed-core and suspended-core microstructured optical fibers). Both fiber-based platforms retains high selectivity of ion binding associated with a small molecule sensor, while also allowing nanoliter volume sampling and on/off switching. We have demonstrated that multiple measurements can be made on a single sample without the need to change the sensor. The ability of the new sensing platform to sense Zn2+ in pleural lavage and nasopharynx of mice was compared to that of established ion sensing methodologies such as inductively coupled plasma mass spectrometry (ICP-MS) and a commercially available fluorophore (Fluozin-3), where the optical-fiber-based sensor provides a significant advantage in that it allows the use of nanoliter (nL) sampling when compared to ICP-MS (mL) and FluoZin-3 (μL). This work paves the way to a generic approach for developing surface-based ion sensors using a range of sensor molecules, which can be attached to a surface without the need for its chemical modification and presents an opportunity for the development of new and highly specific ion sensors for real time sensing applications.
The paper is available online.
21 March 2016:
CNBP researchers Daniel Stubing, Sabrina Heng and Andrew Abell recently published a full paper in the journal ‘Organic and Biomolecular Chemistry’.
The published work presents three new spiropyran photoswitchable sensors and compares their sensitivity to different monovalent metal ions to develop a new reversible lithium ion sensor. These sensing molecules are now able to be further used to create optical devices for the sensing of biological lithium ions, which could help further understanding and treatment of neurological diseases such as manic-depressive illness.
Title: Crowned spiropyran fluoroionophores with a carboxyl moiety for the selective detection of lithium ions
Authors: D. B. Stubing, S. Heng and A. D. Abell
Abstract: The absorbance and fluorescence spectra of carboxylated spiropyrans containing methyl-1-aza-12-crown-4, methyl-1-aza-15-crown-5, methyl-1-aza-18-crown-6 moieties are compared. Characteristic changes in spectra after addition of the alkali metal salts of Li+, Na+, K+ and Cs+ were observed. Chromism induced by the binding of the metal cations was observed as an increase in absorbance and fluorescence. Of these metal cations, the Li+ ion produced the largest change in all three spiropyran systems. Reversible photoswitching of the spiropyran-metal complexes was observed on irradiation with alternating 352 nm UV and white light. This results in reversible fluorescence based sensing of lithium ions with potential for use in a biological sensor device.
The paper is accessible online.
25 February 2016:
Andrew Abell, Professor at the University of Adelaide and Chief Investigator at the CNBP, has recently been elected as an Australian Fulbright Ambassador, a prestigious honour awarded by the Australian-American Fulbright Commission.
The Commission promotes educational and cultural exchange between Australia and the United States in order to enhance mutual understanding and strengthen relations between the two countries. This is primarily achieved through a program of Fulbright Scholarships to support research and study by Australians in the United States and by Americans in Australia.
Professor Abell undertook his first function as Ambassador (the Fulbright Scholar Presentation Evening) on 25 February 2016 at the RACV Club in Melbourne where a distinguished group of Sponsors, Partners, the Board of Directors, other stakeholders, Alumni and representatives of the Australian and US Governments were in attendance. This was a signature event within the Fulbright calendar, formally introducing the newest scholars to the community.
Caption: Prof Andrew Abell, Australian Fulbright Ambassador (Front row, fourth from right).