Sussex Research Laboratories Inc.

Ottawa, Canada

Sussex Research Laboratories Inc.

Ottawa, Canada
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Kennedy A.E.,Laurentian University | Vohra R.,Sussex Research Laboratories Inc. | Scott J.A.,Laurentian University
Sensing and Bio-Sensing Research | Year: 2017

The study of the interactions between a drug and plasma serum proteins are necessary in determining pharmacological and toxicological properties for therapeutic development. Small molecule nerve growth factor (NGF) inhibitors have been investigated for their abilities to inhibit NGF binding to TrkA as a potential therapeutic option for the treatment of neuropathic and inflammatory pain. In this study, surface plasmon resonance (SPR) spectroscopy and 125I-NGF radioisotope binding assays were carried out to better understand the role of serum albumin (SA) in small molecule binding to NGF. SA has been characterized as a universal drug carrier with up to seven binding domains on its surface to transport drug molecules to target tissues. Here, we use SPR kinetic analysis to analyze the change in specificity of small molecules to immobilized NGF in the presence and absence of SA. In the presence of SA an overall increase in small molecule binding affinity for NGF was observed compared to binding in the absence of SA. Our results suggest a crucial role for SA in the pharmacokinetics of small molecule binding to NGF. This effect will require consideration when developing therapeutic agents. © 2017


Sheffield K.S.A.,Laurentian University | Vohra R.,Sussex Research Laboratories Inc. | Scott J.A.,Laurentian University | Ross G.M.,Laurentian University
Pharmacological Research | Year: 2016

Nerve growth factor (NGF), a member of the neurotrophin family, acts to influence the survival and differentiation of neurons in both the central and peripheral nervous systems via its binding to the p75NTR and TrkA receptors. Its precursor, proNGF, has been shown to be the dominant form of NGF in the central nervous system, suggesting a biological function beyond its role as a precursor. Like NGF, proNGF is known to bind the p75NTR receptor. The dysregulation of both NGF and proNGF have been implicated in several pathologies, including neurodegenerative diseases linked to p75NTR-mediated apoptotic signaling. Therefore, the identification of small molecule inhibitors capable of inhibiting both NGF and proNGF-p75NTR interactions may be of therapeutic interest. In the present study, we examine the inhibitory action of known small molecule-based inhibitors PD90780, ALE-0540, Ro 08-2750, and PQC 083, as well as novel derivatives of these compounds, using surface plasmon resonance (SPR) spectroscopy. © 2015 Published by Elsevier Ltd.


Yalagala R.S.,Brock University | Mazinani S.A.,Brock University | Maddalena L.A.,Brock University | Stuart J.A.,Brock University | And 2 more authors.
Carbohydrate Research | Year: 2016

BODIPY fluorophores bearing azide or terminal alkyne functions were conjugated with glycans modified with terminal alkyne or azido through the Cu(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) chemistry under microwave heating while these reactions did not proceed when heated in an oil-bath. The BODIPY-glycan conjugate product 8a undergoes self-assembly into liposomes when hydrated. Formation of liposomes was confirmed by both bright field and confocal microscopy. Fluorescent emission within the liposome was shifted from green to red due to effective high concentrations. © 2016 Elsevier Ltd.


Yan H.,Brock University | Yalagala R.S.,Brock University | Yan F.,Sussex Research Laboratories Inc.
Glycoconjugate Journal | Year: 2015

This review summarises the literature on the synthesis and applications of fluorescently labelled carbohydrates. Due to the sensitivity of fluorescent detection, this approach provides a useful tool to study processes involving glycans. A few general categories of labelling are presented, in situ labelling of carbohydrates with fluorophores, fluorescently labelled glycolipids, fluorogenic glycans, pre-formed fluorescent glycans for intracellular applications, glycan-decorated fluorescent polymers, fluorescent glyconanoparticles, and other functional fluorescent glycans. © 2015 Springer Science+Business Media New York.


Vohra M.,Sussex Research Laboratories Inc. | Sandbhor M.,Sussex Research Laboratories Inc. | Wozniak A.,Sussex Research Laboratories Inc.
Journal of Labelled Compounds and Radiopharmaceuticals | Year: 2015

Hydroxyzine and aripiprazole are active pharmaceutical ingredients that have been largely acknowledged for their antipsychotic properties. Deuterium labeled isotopes of hydroxyzine and aripiprazole are internal standards that can aid in the further research of non-isotopic forms via quantification analysis using HPLC-MS/MS. The synthesis of hydroxyzine-d8 was accomplished by coupling piperazine-d8 with 4-chlorobenzhydryl chloride followed by the reaction of the first intermediate with 2-(2-chloroethoxy) ethanol to afford 11.7% of hydroxyzine-d8 with 99.5% purity. The synthesis of aripiprazole-d8 was also achieved in two steps. 1,4-Dibromobutane-d8 reacted with 7-hydroxy-3,4-dihydro-2(1H)-quinolinone. The first intermediate was then coupled with 1-(2, 3-dichlorophenyl)piperazine hydrochloride to produce 33.4% of aripiprazole-d8 with 99.93% purity. © 2015 John Wiley & Sons, Ltd.


PubMed | Brock University and Sussex Research Laboratories Inc.
Type: Journal Article | Journal: Glycoconjugate journal | Year: 2015

This review summarises the literature on the synthesis and applications of fluorescently labelled carbohydrates. Due to the sensitivity of fluorescent detection, this approach provides a useful tool to study processes involving glycans. A few general categories of labelling are presented, in situ labelling of carbohydrates with fluorophores, fluorescently labelled glycolipids, fluorogenic glycans, pre-formed fluorescent glycans for intracellular applications, glycan-decorated fluorescent polymers, fluorescent glyconanoparticles, and other functional fluorescent glycans.


PubMed | Sussex Research Laboratories Inc.
Type: Journal Article | Journal: Journal of labelled compounds & radiopharmaceuticals | Year: 2015

Hydroxyzine and aripiprazole are active pharmaceutical ingredients that have been largely acknowledged for their antipsychotic properties. Deuterium labeled isotopes of hydroxyzine and aripiprazole are internal standards that can aid in the further research of non-isotopic forms via quantification analysis using HPLC-MS/MS. The synthesis of hydroxyzine-d8 was accomplished by coupling piperazine-d8 with 4-chlorobenzhydryl chloride followed by the reaction of the first intermediate with 2-(2-chloroethoxy) ethanol to afford 11.7% of hydroxyzine-d8 with 99.5% purity. The synthesis of aripiprazole-d8 was also achieved in two steps. 1,4-Dibromobutane-d8 reacted with 7-hydroxy-3,4-dihydro-2(1H)-quinolinone. The first intermediate was then coupled with 1-(2, 3-dichlorophenyl)piperazine hydrochloride to produce 33.4% of aripiprazole-d8 with 99.93% purity.


PubMed | Brock University and Sussex Research Laboratories Inc.
Type: | Journal: Carbohydrate research | Year: 2016

BODIPY fluorophores bearing azide or terminal alkyne functions were conjugated with glycans modified with terminal alkyne or azido through the Cu(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) chemistry under microwave heating while these reactions did not proceed when heated in an oil-bath. The BODIPY-glycan conjugate product 8a undergoes self-assembly into liposomes when hydrated. Formation of liposomes was confirmed by both bright field and confocal microscopy. Fluorescent emission within the liposome was shifted from green to red due to effective high concentrations.

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