Author
Paul S. Donnelly
Other affiliations: University of Western Australia, University of Cambridge, University of Oxford ...read more
Bio: Paul S. Donnelly is an academic researcher from University of Melbourne. The author has contributed to research in topics: Biodistribution & Rhenium. The author has an hindex of 45, co-authored 202 publications receiving 6785 citations. Previous affiliations of Paul S. Donnelly include University of Western Australia & University of Cambridge.
Topics: Biodistribution, Rhenium, Neurodegeneration, Copper, Chemistry
Papers published on a yearly basis
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TL;DR: This critical review presents an historical perspective of Cu(II) complexes progression from potential chemotherapeutics through to more recent applications in nuclear medicine and more recent investigations into their potential as therapeutics for Alzheimer's disease.
Abstract: The molecules known as bis(thiosemicarbazones) derived from 1,2-diones can act as tetradentate ligands for Cu(II), forming stable, neutral complexes. As a family, these complexes possess fascinating biological activity. This critical review presents an historical perspective of their progression from potential chemotherapeutics through to more recent applications in nuclear medicine. Methods of synthesis are presented followed by studies focusing on their potential application as anti-cancer agents and more recent investigations into their potential as therapeutics for Alzheimer's disease. The Cu(II) complexes are of sufficient stability to be used to coordinate copper radioisotopes for application in diagnostic and therapeutic radiopharmaceuticals. Detailed understanding of the coordination chemistry has allowed careful manipulation of the metal based properties to engineer specific biological activities. Perhaps the most promising complex radiolabelled with copper radioisotopes to date is Cu(II)(atsm), which has progressed to clinical trials in humans (162 references).
242 citations
TL;DR: It is demonstrated that increasing intracellular copper bioavailability can restore cognitive function by inhibiting the accumulation of neurotoxic Aβ trimers and phosphorylated tau.
Abstract: Cognitive decline in Alzheimer's disease (AD) involves pathological accumulation of synaptotoxic amyloid-beta (Abeta) oligomers and hyperphosphorylated tau. Because recent evidence indicates that glycogen synthase kinase 3beta (GSK3beta) activity regulates these neurotoxic pathways, we developed an AD therapeutic strategy to target GSK3beta. The strategy involves the use of copper-bis(thiosemicarbazonoto) complexes to increase intracellular copper bioavailability and inhibit GSK3beta through activation of an Akt signaling pathway. Our lead compound Cu(II)(gtsm) significantly inhibited GSK3beta in the brains of APP/PS1 transgenic AD model mice. Cu(II)(gtsm) also decreased the abundance of Abeta trimers and phosphorylated tau, and restored performance of AD mice in the Y-maze test to levels expected for cognitively normal animals. Improvement in the Y-maze correlated directly with decreased Abeta trimer levels. This study demonstrates that increasing intracellular copper bioavailability can restore cognitive function by inhibiting the accumulation of neurotoxic Abeta trimers and phosphorylated tau.
240 citations
TL;DR: While all the macrocyclic bifunctional chelators are suitable for molecular imaging using (64)Cu-labeled antibody conjugates, NOTA and sar-CO2H show significant advantages over the others in that they can be radiolabeled rapidly at room temperature, under dilute conditions, resulting in high specific activity.
197 citations
TL;DR: The CuI complex of the ' click' ligand tris(benzyltriazolylmethyl)amine is an unusual dinuclear dication with one triazole unit bridging two metal centers, and is an effective catalyst for the 'click' cycloaddition reaction.
181 citations
TL;DR: It is demonstrated that MII(btsc) complexes have potential for Alzheimer disease therapy and a role for alternative metal-induced Aβ metabolism has not been ruled out.
178 citations
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TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.
Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …
33,785 citations
28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: The history of the development of PEGylated nanoparticle formulations for systemic administration is described, including how factors such as PEG molecular weight, PEG surface density, nanoparticle core properties, and repeated administration impact circulation time.
2,465 citations
1,904 citations
TL;DR: It is shown that the full set of hydromagnetic equations admit five more integrals, besides the energy integral, if dissipative processes are absent, which made it possible to formulate a variational principle for the force-free magnetic fields.
Abstract: where A represents the magnetic vector potential, is an integral of the hydromagnetic equations. This -integral made it possible to formulate a variational principle for the force-free magnetic fields. The integral expresses the fact that motions cannot transform a given field in an entirely arbitrary different field, if the conductivity of the medium isconsidered infinite. In this paper we shall show that the full set of hydromagnetic equations admit five more integrals, besides the energy integral, if dissipative processes are absent. These integrals, as we shall presently verify, are I2 =fbHvdV, (2)
1,858 citations