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.

Charge transfer in helical peptides

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.

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.

CNBP takes centre stage at Biofocus Conference

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.

 

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).

Latest CNBP review paper explores peptide-based macrocycles

Michelle-Zhang_1_sq10 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.

 

Peptidomimetic boronates as proteasome inhibitors

Michelle-Zhang_1_sq13 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.