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Articles 1 - 12 of 12
Full-Text Articles in Physical Sciences and Mathematics
Poly(2-Alkylacrylic Acid) Polymers Deliver Molecules To The Cytosol By Ph-Sensitive Disruption Of Endosomal Vesicles, Rachel A. Jones, C. Y. Cheung, F. E. Black, J. K. Zia, P. S. Stayton, A. S. Hoffman, Mark R. Wilson
Poly(2-Alkylacrylic Acid) Polymers Deliver Molecules To The Cytosol By Ph-Sensitive Disruption Of Endosomal Vesicles, Rachel A. Jones, C. Y. Cheung, F. E. Black, J. K. Zia, P. S. Stayton, A. S. Hoffman, Mark R. Wilson
Faculty of Science - Papers (Archive)
The permeability barrier posed by cell membranes represents a challenge for the delivery of hydrophilic molecules into cells. We previously proposed that poly(2- alkylacrylic acid)s are endocytosed by cells into acidified vesicles and are there triggered by low pH to disrupt membranes and release the contents of endosomes/lysosomes to the cytosol. If this hypothesis is correct, these polymers could be valuable in drug delivery applications. This report provides functional comparisons of a family of three poly(2-alkylacrylic acid)s. Poly(2-propylacrylic acid) (PPAA), poly(2-ethylacrylic acid) (PEAA), and poly(2-methylacrylic acid) (PMAA) were compared in red blood cell haemolysis assays and in a lipoplex gene …
Novel Pharmacophore Based Methods Reveal Gossypol As A Reverse Transcriptase Inhibitor, Paul A. Keller, C. Birch, S. P. Leach, D. Tyssen, R. Griffith
Novel Pharmacophore Based Methods Reveal Gossypol As A Reverse Transcriptase Inhibitor, Paul A. Keller, C. Birch, S. P. Leach, D. Tyssen, R. Griffith
Faculty of Science - Papers (Archive)
In a program to identify new structural entities for the inhibition of the HIV-1 reverse transcriptase (RT) enzyme via database searching, a series of RT pharmacophores were developed. By utilising a novel filtering technique, the National Cancer Institute database of compounds was scanned producing 15 compounds to be screened for activity. A notable inclusion was a series of gossypol derivatives. The testing of a series of compounds revealed the parent compound gossypol to be an HIV-1 reverse transcriptase inhibitor. These results suggest that at least part of its anti-HIV activity is due to gossypol targeting the non-nucleoside inhibitor binding pocket …
Probing Dna Selectivity Of Ruthenium Metallointercalators Using Esi Mass Spectrometry, Jennifer L. Beck, Rajesh Gupta, Thitima Urathamakul, Nyree L. Williamson, Margaret Sheil, Janice Aldrich-Wright, Stephen F. Ralph
Probing Dna Selectivity Of Ruthenium Metallointercalators Using Esi Mass Spectrometry, Jennifer L. Beck, Rajesh Gupta, Thitima Urathamakul, Nyree L. Williamson, Margaret Sheil, Janice Aldrich-Wright, Stephen F. Ralph
Faculty of Science - Papers (Archive)
ESI mass spectra show that up to five ruthenium molecules can bind non-covalently to double stranded 16mer DNA, and provide information on the relative affinity and DNA sequence selectivity of different ruthenium complexes.
Evolution Of Chemical Contaminant And Toxicology Studies, Part 2- Case Studies Of Selenium And Arsenic, Glennys O'Brien, Dianne Jolley, Robert John Morrison
Evolution Of Chemical Contaminant And Toxicology Studies, Part 2- Case Studies Of Selenium And Arsenic, Glennys O'Brien, Dianne Jolley, Robert John Morrison
Faculty of Science - Papers (Archive)
As the second of a two part series discussing the evolution of the field of environmental toxicology, this paper presents two case studies: selenium and arsenic. Developments over several decades in the understanding of the behaviour of arsenic and selenium in different chemical forms in various compartments of the environment are discussed. Selenium was initially thought to be toxic, but later investigations showed it to be an essential micronutrient with a variety of biochemical functions, and, importantly, that there is a very narrow gap between the essential and the toxic body burden. Arsenic, on the other hand, has not yet …
Asymmetric Synthesis Of (-)-7-Epiaustraline And (+)-1,7-Diepiaustraline, Minyan Tang, Stephen G. Pyne
Asymmetric Synthesis Of (-)-7-Epiaustraline And (+)-1,7-Diepiaustraline, Minyan Tang, Stephen G. Pyne
Faculty of Science - Papers (Archive)
A diastereoselective and modular approach to the synthesis of the 3-hydroxymethyl-2,3,5,6,7,7a-hexahydro-1H-pyrrolizine-1,2,7-triol structure, characteristic of several natural pyrrolizidine natural products has been developed. This approach culminated in the synthesis of (-)-7-epiaustraline and (+)-1,7-diepiaustraline. The oxazolidinone group has been found to be a useful protecting group in the RCM reaction and, as part of a pyrrolo[1,2-c]oxazol-3-one ring system, has functioned as a stereo- and regio-directing group, in a key diastereoselective cis-dihydroxylation reaction and a regioselective nucleophilic ring-opening of a S,S-dioxo-dioxathiole.
Chemo-Enzymatic Synthesis Of (-)-Epipentenomycin I, Tawesin Klomklao, Stephen G. Pyne, Apiwat Baramee, Brian W. Skelton, Allan H. White
Chemo-Enzymatic Synthesis Of (-)-Epipentenomycin I, Tawesin Klomklao, Stephen G. Pyne, Apiwat Baramee, Brian W. Skelton, Allan H. White
Faculty of Science - Papers (Archive)
A chemo-enzymatic synthesis of (−)-epipentenomycin I is reported using a lipase-catalysed kinetic resolution of the racemic pentacyclic alcohol 8. Flash vacuum pyroloysis of (−)-8 so obtained gave (−)-(4R)-4-hydroxy-5-methylene-2-cyclopentenone. Epoxidation of this compound with dimethyldioxirane followed by hydrolytic ring-opening of the resulting epoxide gave (−)-epipentenomycin I.
The Prevention Of Preterm Labour – Corticotropin Releasing Hormone Type 1 Receptors As A Target For Drug Design And Development, Paul A. Keller, K. Kirkwood, J. Morgan, S. Westcott, A. Mccluskey
The Prevention Of Preterm Labour – Corticotropin Releasing Hormone Type 1 Receptors As A Target For Drug Design And Development, Paul A. Keller, K. Kirkwood, J. Morgan, S. Westcott, A. Mccluskey
Faculty of Science - Papers (Archive)
The role of the corticotropin releasing hormone in the onset of labour and the subsequent medicinal chemistry implications of CRH antagonists for the prevention of premature birth, and identification of the CRH type 1 receptor as the target for this drug design, are reviewed here.
Development Of A Simple, Self-Consistent Polarizable Model For Liquid Water, Haibo Yu, Tomas Hansson, Wilfred Van Gunsteren
Development Of A Simple, Self-Consistent Polarizable Model For Liquid Water, Haibo Yu, Tomas Hansson, Wilfred Van Gunsteren
Faculty of Science - Papers (Archive)
The charge-on-spring method is used to develop a rigid, three-site, polarizable water model, a noniterative and a self-consistent version. In this method, the polarizability is taken into account by a variable separation of charges on selected polarizable centers. One of the pair of polarization charges resides on a polarizable center, while the other one is treated as an additional particle attached to the polarizable center by a parabolic restraint potential. The separation is calculated in response to the instantaneous electric field. We parametrized two models which are based on noniterative and self-consistent versions of the method, respectively. We computed several …
Tyrosine Phosphorylation Of Hsp-90 During Mammalian Sperm Capacitation, Heath W. Ecroyd, Russell C. Jones, Robert J. Aitken
Tyrosine Phosphorylation Of Hsp-90 During Mammalian Sperm Capacitation, Heath W. Ecroyd, Russell C. Jones, Robert J. Aitken
Faculty of Science - Papers (Archive)
The process of sperm capacitation is correlated with activation of a signal transduction pathway leading to protein tyrosine phosphorylation. Whereas phosphotyrosine expression is an essential prerequisite for fertilization, the proteins that are phosphorylated during capacitation have not yet been identified. In the present study, we observed that a major target of this signaling pathway is the molecular chaperone protein, heat shock protein (HSP)-86, a member of the HSP-90 family of HSPs. We used cross-immunoprecipitation experiments to confirm the tyrosine phosphorylation of HSP-86, a process that is not inhibited by the ansamycin antibiotic, geldanamycin. The general significance of these findings was …
Endogenous Redox Activity In Mouse Spermatozoa And Its Role In Regulating The Tyrosine Phosphorylation Events Associated With Sperm Capacitation, Heath W. Ecroyd, Russell C. Jones, Robert J. Aitken
Endogenous Redox Activity In Mouse Spermatozoa And Its Role In Regulating The Tyrosine Phosphorylation Events Associated With Sperm Capacitation, Heath W. Ecroyd, Russell C. Jones, Robert J. Aitken
Faculty of Science - Papers (Archive)
We investigated the role of endogenous redox activity in regulating the signal transduction pathway leading to tyrosine phosphorylation in mouse spermatozoa. Endogenous redox activity was monitored using a luminol-peroxidase chemiluminescent probe. Chemiluminescence increased in spermatozoa that were actively undergoing cAMP-mediated tyrosine phosphorylation events associated with capacitation and was inhibited in a dose-dependent manner by addition of catalase or diphenylene iodonium, both of which also inhibited tyrosine phosphorylation within the cell at points downstream of cAMP. Excluding bicarbonate from the incubation medium reduced the redox activity of sperm by 80-90% and dramatically reduced tyrosine phosphorylation. This study provides the first evidence …
Evolution Of Chemical Contaminant And Toxicology Studies, Part 1 - An Overview, Dianne F. Jolley, Glennys A. O'Brien, Robert John Morrison
Evolution Of Chemical Contaminant And Toxicology Studies, Part 1 - An Overview, Dianne F. Jolley, Glennys A. O'Brien, Robert John Morrison
Faculty of Science - Papers (Archive)
The study of environmental chemical contaminants and their toxicological effects has changed dramatically over the last 50 years. Initially studies concentrated on trying to identify what contaminants were actually present and to develop quantitative methods to determine the concentrations (total) present. Health impacts were often investigated independently in medical research centres. With improving analytical techniques, studies of the speciation of contaminants began and the specific forms that were creating the major problems were gradually identified. Continuing improvements in analytical chemistry, together with a move towards more integrated and multidisciplinary research now sees chemists, biologists, toxicologists and health researchers working closely …
Stemocurtisine, The First Pyrido[1,2-A]Azapine Stemona Alkaloid, Pitchaya Mungkornasawakul, Stephen G. Pyne, Araya Jatisatienr, Damrat Supyen, Wilford Lie, Alison T. Ung, Brian W. Skelton, Allan H. White
Stemocurtisine, The First Pyrido[1,2-A]Azapine Stemona Alkaloid, Pitchaya Mungkornasawakul, Stephen G. Pyne, Araya Jatisatienr, Damrat Supyen, Wilford Lie, Alison T. Ung, Brian W. Skelton, Allan H. White
Faculty of Science - Papers (Archive)
A new pentacyclic stemona alkaloid, stemocurtisine (2), with a novel pyrido[1,2-a]azapine A,B-ring system, has been isolated from a root extract of Stemona curtisii. The structure and relative stereochemistry was determined by spectral data interpretation and X-ray crystallography.