Mostyn, SN, Carland, JE, Shimmon, S, Ryan, RM, Rawling, T & Vandenberg, RJ 2017, 'Synthesis and Characterization of Novel Acyl-Glycine Inhibitors of GlyT2.', ACS Chemical Neuroscience, vol. 8, no. 9, pp. 1949-1959.View/Download from: UTS OPUS or Publisher's site
It has been demonstrated previously that the endogenous compound N-arachidonyl-glycine inhibits the glycine transporter GlyT2, stimulates glycinergic neurotransmission, and provides analgesia in animal models of neuropathic and inflammatory pain. However, it is a relatively weak inhibitor with an IC50 of 9 μM and is subject to oxidation via cyclooxygenase, limiting its therapeutic value. In this paper we describe the synthesis and testing of a novel series of monounsaturated C18 and C16 acyl-glycine molecules as inhibitors of the glycine transporter GlyT2. We demonstrate that they are up to 28 fold more potent that N-arachidonyl-glycine with no activity at the closely related GlyT1 transporter at concentrations up to 30 μM. This novel class of compounds show considerable promise as a first generation of GlyT2 transport inhibitors.
King, SR, Shimmon, S, Totonjian, DD & McDonagh, AM 2017, 'Influence of Bound versus Non-Bound Stabilizing Molecules on the Thermal Stability of Gold Nanoparticles', Journal of Physical Chemistry C, vol. 121, no. 25, pp. 13944-13951.View/Download from: UTS OPUS or Publisher's site
© 2017 American Chemical Society. Knowledge concerning the sintering behavior of gold nanoparticles (AuNPs) allows for improved nanomaterials for applications such as printed electronics, catalysis and sensing. In this study, we examined the ability of a range of compounds to stabilize AuNPs against thermal sintering and compared compounds with and without functional groups that anchor the molecules to the nanoparticle surface. Thermal stability was characterized in terms of the temperature of the sintering event (T SE ) as well as thermogravimetric analysis and scanning electron microscopy. We show that anchored stabilizing compounds with high thermal stability are effective at preventing the sintering of AuNPs until the decomposition of the compound. A T SE of 390 °C was achieved using 1-pyrenebutanethiol as stabilizer. Of the unanchored stabilizers, which were combined with butanethiol-capped AuNPs, two were found to be particularly effective: oleylamine (T SE ≈ 300 °C) and a perylenedicarboximide derivative (T SE ≈ 540 °C), the latter conferring an unprecedented level of thermal stability on ligand-stabilized AuNPs. When selecting stabilizers without anchoring groups, our results demonstrate the importance of choosing those that have an affinity with the capping ligands on the AuNPs to ensure a uniform mixture of AuNPs and stabilizer within a film.
Wu, J, Shimmon, S, Paton, S, Daly, C, Goldschlager, T, Gronthos, S, Zannettino, ACW & Ghosh, P 2017, 'Pentosan polysulfate binds to STRO-1+mesenchymal progenitor cells, is internalized, and modifies gene expression: A novel approach of pre-programing stem cells for therapeutic application requiring their chondrogenesis', Stem Cell Research and Therapy, vol. 8, no. 1, pp. 1-15.View/Download from: UTS OPUS or Publisher's site
© 2017 The Author(s). Background: The pharmaceutical agent pentosan polysulfate (PPS) is known to induce proliferation and chondrogenesis of mesenchymal progenitor cells (MPCs) in vitro and in vivo. However, the mechanism(s) of action of PPS in mediating these effects remains unresolved. In the present report we address this issue by investigating the binding and uptake of PPS by MPCs and monitoring gene expression and proteoglycan biosynthesis before and after the cells had been exposed to limited concentrations of PPS and then re-established in culture in the absence of the drug (MPC priming). Methods: Immuno-selected STRO-1 + mesenchymal progenitor stem cells (MPCs) were prepared from human bone marrow aspirates and established in culture. The kinetics of uptake, shedding, and internalization of PPS by MPCs was determined by monitoring the concentration-dependent loss of PPS media concentrations using an enzyme-linked immunosorbent assay (ELISA) and the uptake of fluorescein isothiocyanate (FITC)-labelled PPS by MPCs. The proliferation of MPCs, following pre-incubation and removal of PPS (priming), was assessed using the Wst-8 assay method, and proteoglycan synthesis was determined by the incorporation of 35 SO 4 into their sulphated glycosaminog lycans. The changes in expression of MPC-related cell surface antigens of non-primed and PPS-primed MPCs from three donors was determined using flow cytometry. RNA sequencing of RNA isolated from non-primed and PPS-primed MPCs from the same donors was undertaken to identify the genes altered by the PPS priming protocol. Results: The kinetic studies indicated that, in culture, PPS rapidly binds to MPC surface receptors, followed by internalisation and localization within the nucleus of the cells. Following PPS-priming of MPCs and a further 48 h of culture, both cell proliferation and proteoglycan synthesis were enhanced. Reduced expression of MPC-related cell surface antigen expression was promoted by the PPS priming, ...
King, SR, Shimmon, S, Gentle, AR, Westerhausen, MT, Dowd, A & McDonagh, AM 2016, 'Remarkable thermal stability of gold nanoparticles functionalised with ruthenium phthalocyanine complexes', NANOTECHNOLOGY, vol. 27, no. 21.View/Download from: UTS OPUS or Publisher's site
Oehme, D, Ghosh, P, Shimmon, S, Wu, J, McDonald, C, Troupis, JM, Goldschlager, T, Rosenfeld, JV & Jenkin, G 2014, 'Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model', JOURNAL OF NEUROSURGERY-SPINE, vol. 20, no. 6, pp. 657-669.View/Download from: Publisher's site
Ghosh, P, Wu, J, Shimmon, S, Zannettino, ACW, Gronthos, S & Itescu, S 2010, 'Pentosan polysulfate promotes proliferation and chondrogenic differentiation of adult human bone marrow-derived mesenchymal precursor cells', ARTHRITIS RESEARCH & THERAPY, vol. 12, no. 1.View/Download from: Publisher's site
Ghosh, P, Shimmon, S, Wilson-Ghosh, N & Whitehouse, M 2008, 'CARTILAGE DERIVED PEPTACANS: NOVEL NUTRACEUTICALS WITH IMMUNOMODULATORY, ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES', CURRENT TOPICS IN NUTRACEUTICAL RESEARCH, vol. 6, no. 2, pp. 83-98.
Ghosh, P, Shimmon, S & Whitehouse, MW 2006, 'Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: A novel approach to therapy', Inflammopharmacology, vol. 14, no. 3-4, pp. 155-162.View/Download from: Publisher's site
Molecular fragments of cartilage are antigenic and can stimulate an autoimmune response. Oral administration of type II collagen prevents disease onset in animal models of arthritis but the effects of other matrix components have not been reported. We evaluated glycosaminoglycan polypeptides (GAG-P) and matrix proteins (CaP) from cartilage for a) mitigating disease activity in rats with collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) and b) stimulating proteoglycan (PG) synthesis by chondrocytes in-vitro. CIA and AIA were established in Wistar rats using standard methods. Agents were administered orally (10-200 mg/kg), either for seven days prior to disease induction (toleragenic protocol), or continuously for 15 days after injecting the arthritigen (prophylactic protocol). Joint swelling and arthritis scores were determined on day 15. Histological sections of joint tissues were assessed post-necropsy. In chondrocyte cultures, CaP +/- interleukin-1 stimulated PG biosynthesis. CaP was also active in preventing arthritis onset at 3.3, 10 or 20mg/kg in the rat CIA model using the toleragenic protocol. It was only active at 20 and 200 mg/kg in the CIA prophylactic protocol. GAG-P was active in the CIA toleragenic protocol at 20mg/kg but chondroitin sulfate and glucosamine hydrochloride or glucosamine sulfate were all inactive. The efficacy of CaP in the rat AIA model was less than in the CIA model. These findings lead us to suggest that oral CaP could be used as a disease-modifying anti-arthritic drug. © Birkhäuser Verlag, Basel 2006.
Shen, BJ, Shimmon, S, Smith, MM & Ghosh, P 2003, 'Biosensor analysis of the molecular interactions of pentosan polysulfate and of sulfated glycosaminoglycans with immobilized elastase, hyaluronidase and lysozyme using surface plasmon resonance (SPR) technology', JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, vol. 31, no. 1, pp. 83-93.View/Download from: Publisher's site
Ghosh, P, Shimmon, S & Whitehouse, M 2005, 'Arthritic disease suppression by oral tolerization with glycosaminoglycan peptide complexes derived from the cartilage extracellular matrix', INFLAMMATION RESEARCH, BIRKHAUSER VERLAG AG, pp. S118-S118.
Ghosh, P, Shimmon, S & Whitehouse, M 2004, 'A novel glycosaminoglycan polypeptide complex, peptacan, suppresses joint inflammation and preserves cartilage in rat models of arthritis given orally either as a toleragen or as a therapeutic agent', OSTEOARTHRITIS AND CARTILAGE, 9th World Congress of the Osteoarthritis-Research-Society-International, W B SAUNDERS CO LTD, Chicago, IL, pp. S77-S77.