Tag Archives: Andrew Abell

Peptides as bio-inspired electronic materials

7 September 2018:

A new paper with CNBP authors Jingxian Yu, John Horsley and Andrew Abell extends fundamental knowledge of charge transfer dynamics and kinetics in peptides and also open up new avenues to design and develop functional bio-inspired electronic devices, such as on/off switches and quantum interferometers, for practical applications in molecular electronics.

Journal: Accounts of Chemical Research.

Publication title: Peptides as Bio-Inspired Electronic Materials: An Electrochemical and First-Principles Perspective.

Authors: Jingxian Yu, John R. Horsley, and Andrew D. Abell.

Abstract: Molecular electronics is at the forefront of interdisciplinary research, offering a significant extension of the capabilities of conventional silicon-based technology as well as providing a possible stand-alone alternative. Bio-inspired molecular electronics is a particularly intriguing paradigm, as charge transfer in proteins/peptides, for example, plays a critical role in the energy storage and conversion processes for all living organisms. However, the structure and conformation of even the simplest protein is extremely complex, and therefore, synthetic model peptides comprising well-defined geometry and predetermined functionality are ideal platforms to mimic nature for the elucidation of fundamental biological processes while also enhancing the design and development of single-peptide electronic components.

In this Account, we first present intramolecular electron transfer within two synthetic peptides, one with a well-defined helical conformation and the other with a random geometry, using electrochemical techniques and computational simulations. This study reveals two definitive electron transfer pathways (mechanisms), the natures of which are dependent on secondary structure. Following on from this, electron transfer within a series of well-defined helical peptides, constrained by either Huisgen cycloaddition, ring-closing metathesis, or a lactam bridge, was determined. The electrochemical results indicate that each constrained peptide, in contrast to a linear counterpart, exhibits a remarkable shift of the formal potential to the positive (>460 mV) and a significant reduction of the electron transfer rate constant (up to 15-fold), which represent two distinct electronic “on/off” states. High-level calculations demonstrate that the additional backbone rigidity provided by the side-bridge constraints leads to an increased reorganization energy barrier, which impedes the vibrational fluctuations necessary for efficient intramolecular electron transfer through the peptide backbone. Further calculations reveal a clear mechanistic transition from hopping to superexchange (tunneling) stemming from side-bridge gating. We then extended our research to fine-tuning of the electronic properties of peptides through both structural and chemical manipulation, to reveal an interplay between electron-rich side chains and backbone rigidity on electron transfer. Further to this, we explored the possibility that the side-bridge constraints present in our synthetic peptides provide an additional electronic transport pathway, which led to the discovery of two distinct forms of quantum interferometer. The effects of destructive quantum interference appear essentially through both the backbone and an alternative tunneling pathway provided by the side bridge in the constrained β-strand peptide, as evidenced by a correlation between electrochemical measurements and conductance simulations for both linear and constrained β-strand peptides. In contrast, an interplay between quantum interference effects and vibrational fluctuations is revealed in the linear and constrained 310-helical peptides.

Awards congratulations

28 February, 2018:

Congratulations to the following CNBP students and researchers who were successful at the annual ‘Institute for Photonics and Advanced Sensing (IPAS) Awards’.

  • Jiawen Li (Joint IPAS Best ECR Paper)
  • Team: Patrick Capon, Malcolm Purdey, Benjamin Pullen and Andrew Abell (IPAS Best Transdisciplinary Paper)
  • Kathryn Palasis (Tanya Monro Best Student Oral Presentation)


Antibiotic research featured by the NHMRC

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!

First reversible ‘turn-off’ sensor for Glutathione

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.

Journal: Biosensors.

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.

Sensors for calcium ion

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.

A step towards bio-inspired quantum interferometers

Jingxian Yu_low_sq29 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).

CNBP’s recognize theme expands

Andrew-Abell-224 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!

Photochromic molecules explored in MOF environment

Daniel Stubing High Res Edit 005510 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.

Inhibition of α-chymotrypsin

Michelle-Zhang_1_sq23 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.

Sensing Zn2+ ions in biological samples

sabrina213 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.