A5015410355- Biochemical and Structural Characterization
- Antimicrobial Peptides and Activities
- Nicotinic Acetylcholine Receptors Study
- Chemical Synthesis and Analysis
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Phytoplasmas and Hemiptera pathogens
- Toxin Mechanisms and Immunotoxins
- Click Chemistry and Applications
- Glycosylation and Glycoproteins Research
- Transgenic Plants and Applications
- Molecular spectroscopy and chirality
- Liver Disease and Transplantation
- Liver Disease Diagnosis and Treatment
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Metal complexes synthesis and properties
- Advanced NMR Techniques and Applications
- RNA and protein synthesis mechanisms
- Organophosphorus compounds synthesis
- Nuclear reactor physics and engineering
- Radioactive element chemistry and processing
- Chemical synthesis and alkaloids
- Nuclear Materials and Properties
- DNA and Nucleic Acid Chemistry
ARC Centre of Excellence for Innovations in Peptide and Protein Science
2020-2025
The University of Queensland
2016-2025
Australian Research Council
2020-2025
Brisbane School of Theology
2020
Women's College Hospital
2019
University of Toronto
2019
Griffith University
1994-2015
Shrewsbury and Telford Hospital NHS Trust
2013
Australian National University
1999-2010
University of Alberta
2006
Abstract With the emergence of multidrug-resistant bacteria, antimicrobial peptides (AMPs) offer promising options for replacing traditional antibiotics to treat bacterial infections, but discovering and designing AMPs using methods is a time-consuming costly process. Deep learning has been applied de novo design address AMP classification with high efficiency. In this study, several natural language processing models were combined identify AMPs, i.e. sequence generative adversarial nets,...
We examined the modulation of persistent inward currents (PICs) by serotonin (5-HT) in spinal motoneurons normal and chronic rats. PICs are composed both a TTX-sensitive sodium current (Na PIC) nimodipine-sensitive calcium (Ca PIC), we focused on quantifying Na PIC (and its action total which is known to be critical enabling repetitive firing. Intracellular recordings were made from whole sacrocaudal cord adult rats after was acutely transected at S2 level (acute rat condition), removed...
Cyclotides are plant peptides comprising a circular backbone and three conserved disulfide bonds that confer them with exceptional stability. They were originally discovered in Oldenlandia affinis based on their use traditional African medicine to accelerate labor. Recently, cyclotides have been identified numerous species of the coffee, violet, cucurbit, pea, potato, grass families. Their unique structural topology, high stability, tolerance sequence variation make promising templates for...
Several cyclic peptides have been reported to unexpectedly high membrane permeability. Of these, cyclosporin A is perhaps the most well-known example, particularly in light of its relatively molecular weight. Observations that changes conformation depending on solvent environment led hypothesis conformational dynamics a prerequisite for permeability; however, this has difficult validate experimentally. Here, we use simulations explicitly determine behavior and other related as they...
Significance The α9α10 nicotinic AChR (nAChR) subtype is a recently identified target for the development of breast cancer chemotherapeutics and analgesics, particularly to treat neuropathic pain. Structure/function analyses antagonists this are therefore essential specific therapeutic compounds. Conus genus rich source pharmacologically active peptides, we report here that αO-conotoxin GeXIVA potent selective antagonist nAChR subtype. displays unique structural properties among other...
In the months after spinal cord transection, motoneurons in rat develop large persistent inward currents (PICs) that are responsible for muscle spasticity. These PICs mediated by low-threshold TTX-sensitive sodium (Na PIC) and L-type calcium (Ca PIC). Recently, Na PIC was shown to become supersensitive serotonin (5-HT) chronic injury. present paper, a similar change sensitivity of Ca 5-HT investigated The whole sacrocaudal from acute rats spastic (S2 level transection 2 mo previously)...
Plant defensins are small, cysteine-rich peptides with antifungal activity against a broad range of yeast and fungi. In this study we investigated the antibiofilm plant defensin from coral bells (Heuchera sanguinea), i.e. HsAFP1. To end, HsAFP1 was heterologously produced using Pichia pastoris as host. The recombinant peptide rHsAFP1 showed similar pathogen Fusarium culmorum native purified seeds. NMR analysis revealed that consists an α-helix triple-stranded antiparallel β-sheet stabilised...
Tachyplesin I, II and III are host defense peptides from horseshoe crab species with antimicrobial anticancer activities. They have an amphipathic β-hairpin structure, highly positively-charged differ by only one or two amino acid residues. In this study, we compared the structure activity of three tachyplesin alongside their backbone cyclized analogues. We assessed peptide structures using nuclear magnetic resonance (NMR) spectroscopy, then against bacteria (both in planktonic biofilm...
Pathogenic microbes are developing resistance to established antibiotics, making the development of novel antimicrobial molecules paramount. One major resource for discovery antimicrobials is arsenal innate immunity that part first line pathogen defense in many organisms. Gene encoded cationic peptides a constituent immune arsenals. Many these exhibit potent activity vitro. However, hurdle has impeded their use clinic loss at physiological salt concentrations, attributed weakening...
Fungi are a newly emerging source of peptide antibiotics with therapeutic potential. Here, we report 17 new fungal defensin-like (fDLP) genes and the detailed characterization corresponding synthetic fDLP (micasin) from dermatophyte in terms its structure, activity NMR analysis showed that micasin adopts “hallmark” cysteine-stablized α-helical β-sheet fold. It was active on both Gram-positive Gram-negtive bacteria, importantly it killed two clinical isolates methicillin-resistant...
The α3β4 nAChRs are implicated in pain sensation the PNS and addiction to nicotine CNS. We identified an α-4/6-conotoxin (CTx) TxID from Conus textile. new toxin consists of 15 amino acid residues with two disulfide bonds. was synthesized using solid phase methods, synthetic peptide functionally tested on heterologously expressed Xenopus laevis oocytes. blocked rat a 12.5 nM IC50, which places it among most potent nAChR antagonists. also closely related α6/α3β4 94 IC50 but showed little...
The θ-defensins are, to date, the only known ribosomally synthesized cyclic peptides in mammals, and they have promising antimicrobial bioactivities. characteristic structural motif of is cystine ladder, comprising a peptide backbone three parallel disulfide bonds. In contrast knot, which characterizes plant cyclotides, ladder has not been as well described motif. Here we report solution structures nuclear magnetic resonance relaxation properties aqueous representative from different...
The ICK (inhibitor cystine knot) defines a large superfamily of polypeptides with high structural stability and functional diversity. Here, we describe new scorpion venom-derived K+ channel toxin (named λ-MeuKTx-1) an fold through gene cloning, chemical synthesis, nuclear magnetic resonance spectroscopy, Ca2+ release measurements electrophysiological recordings. λ-MeuKTx-1 was found to adopt that contains three-strand anti-parallel β-sheet 310-helix. Functionally, this peptide selectively...
Multiple sclerosis (MS) is a debilitating disease that requires prolonged treatment with often severe side effects. One experimental MS therapeutic currently under development single amino acid mutant of plant peptide termed kalata B1, the cyclotide family. Like all cyclotides, candidate [T20K]kB1 highly stable as it contains cyclic backbone cross-linked by three disulfide bonds in knot-like structure. This stability much sought after for drugs, which despite exquisite selectivity their...
Abstract The design of disulfide bond mimetics is an important strategy for optimising cysteine‐rich peptides in drug development. Mimetics the lead conotoxin MrIA, which one selectively replaced by a 1,4‐disubstituted‐1,2,3‐triazole bridge, are described. Sequential copper‐catalyzed azide–alkyne cycloaddition (CuAAC; click reaction) followed formation resulted regioselective syntheses triazole–disulfide hybrid MrIA analogues. with triazole replacing Cys4–Cys13 retained tertiary structure...
Abstract Ruthenium‐catalysed azide–alkyne cycloaddition (RuAAC) provides access to 1,5‐disubstituted 1,2,3‐triazole motifs in peptide engineering applications. However, investigation of this motif as a disulfide mimetic cyclic peptides has been limited, and the structural consequences remain be studied. We report synthetic strategies install various triazole linkages into through backbone cyclisation RuAAC cross‐linking reactions. These were evaluated four serine protease inhibitors based on...
μ-Conotoxin KIIIA, a selective blocker of sodium channels, has strong inhibitory activity against several Nav isoforms, including Nav1.7, and potent analgesic effects, but it contains three pairs disulfide bonds, making structural modification difficult synthesis complex. To circumvent these difficulties, we designed synthesized KIIIA analogues with one bond deleted. The most active analogue, KIIIA-1, was further analyzed, its binding pattern to hNav1.7 determined by molecular dynamics...
To assess the public health significance of premature weaning infants from breast milk on later-life risk chronic illness.A review and summary recent meta-analyses studies linking with disease is presented followed by an estimation approximate exposure in a developed Western country, based historical breast-feeding prevalence data for Australia since 1927. The population-attributable proportion associated current patterns artificial feeding infancy estimated.After adjustment major...
Abstract Measurements of self-diffusion in solution-grown single crystals CsCl have been made over the temperature range 200–460°c. Comparison with electrical conductivity measurements indicates that is essentially ionic and anion defects are more mobile. Schottky seem to be predominant type point their formation enthalpy l·86 ev. Activation enthalpies for vacancy mobility estimated 0·6 ev 0·34 cation vacancies respectively. The diffusion cannot completely accounted terms movement it...
Cyclotides are a family of plant defense proteins with unique cyclic backbone and cystine knot. Their remarkable stability under harsh thermal, enzymatic, chemical conditions, combined their range bioactivities, including anti-HIV activity, underpins potential as protein drug scaffolds. The vast majority cyclotides possess conserved glutamate residue in loop 1 the sequence that is involved structurally important network hydrogen bonds to an adjacent (loop 3). A single native cyclotide...