Leonard G Luyt

Leonard G Luyt
The University of Western Ontario | UWO · Department of Chemistry

Ph.D.

About

134
Publications
9,041
Reads
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1,461
Citations
Additional affiliations
July 2005 - present
The University of Western Ontario
Position
  • Professor (Associate)
July 2005 - present
London Regional Cancer Program
Position
  • Senior Scientist
July 2005 - present
Western University
Position
  • Professor

Publications

Publications (134)
Article
Objective One driving factor in the progression to posttraumatic osteoarthritis (PTOA) is the perpetuation of the inflammatory response to injury into chronic inflammation. Molecular imaging offers many opportunities to complement the sensitivity of current imaging modalities with molecular specificity. The goal of this study was to develop and cha...
Article
The growth hormone secretagogue receptor 1a (GHSR) is differentially expressed in various disease states compared to healthy tissues and thus is a target for molecular imaging. The endogenous ligand for the GHSR is ghrelin, a 28 amino acid peptide with a unique octanoyl group on the serine-3 residue. A recently reported ghrelin analogue revealed th...
Preprint
Full-text available
Ghrelin O -acyltransferase (GOAT) plays a central role in the maturation and activation of the peptide hormone ghrelin, which performs a wide range of endocrinological signaling roles. Using a tight-binding fluorescent ghrelin-derived peptide designed for high selectivity for GOAT over the ghrelin receptor GHS-R1a, we demonstrate that GOAT interact...
Article
Glioblastoma (GBM) is the most common and deadliest form of brain tumor and remains amongst the most difficult cancers to treat. Brevican (Bcan), a central nervous system (CNS)‐specific extracellular matrix protein, is upregulated in high‐grade glioma cells, including GBM. A Bcan isoform lacking most glycosylation, dg‐Bcan, is found only in GBM tis...
Article
Full-text available
Background The hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) are expressed in myocardium. GHSR binding activates signalling pathways coupled to cardiomyocyte survival and contractility. These properties have made the ghrelin-GHSR axis a candidate for a biomarker of cardiac function. The dynamics of ghrelin-GHSR a...
Preprint
Full-text available
The hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) are expressed in myocardium. GHSR binding activates signalling pathways coupled to cardiomyocyte survival and contractility. These properties have made the ghrelin-GHSR axis a candidate for a biomarker of cardiac function. The dynamics of ghrelin-GHSR are altered...
Preprint
Full-text available
Background Targeted therapies for malignant brain cancer that are currently available have little clinical activity, highlighting an urgent need for the development of novel precision medicines. Brevican (Bcan), a central nervous system (CNS)-specific extracellular matrix protein is upregulated in glioma cells. A brevican isoform lacking glycosylat...
Article
Full-text available
Two new fluorescence imaging probes have been synthesized by incorporating a versatile alkyne-substituted boron difluoride formazanate precursor with peptides through copper-catalyzed alkyne–azide cycloaddition. The formazanate dye was appended to a C-terminal amino acid of ghrelin for imaging the growth hormone secretagogue receptor (GHSR-1a). To...
Article
A one-bead one-compound (OBOC) library of peptide-based imaging agents was developed where a ¹⁹F-containing moiety was added onto the N-terminus of octamer peptides through copper free-click chemistry prior to screening of the library. This created a library of complete imaging agents which was screened against CXCR4, a receptor of interest for can...
Article
Full-text available
Inflammation plays a critical role in osteoarthritis (OA). It stimulates catabolic events in articular chondrocytes and prevents chondrogenic precursor cells from repairing cartilage lesions, leading to accelerated cartilage degradation. Therefore, the identification of novel factors that reduce catabolic events in chondrocytes and enhances chondro...
Article
Full-text available
The growth hormone secretagogue receptor 1a (GHSR), also called the ghrelin receptor, is a G protein-coupled receptor known to play an important metabolic role in the regulation of various physiological processes, including energy expenditure, growth hormone secretion, and cell proliferation. This receptor has been implicated in numerous health iss...
Article
Full-text available
Proteinase Activated Receptor-4 (PAR4) is a member of the proteolytically-activated PAR family of G-protein-coupled receptor (GPCR) that represents an important target in the development of anti-platelet therapeutics. PARs are activated by proteolytic-cleavage of their receptor N-terminus by enzymes such as thrombin, trypsin, and cathepsin-G. This...
Article
High-grade gliomas are deadly cancers, and current standard-of-care has demonstrated limited success. The ability to specifically target glioma cells allows for the development of safer and more efficacious brain cancer therapy strategies. Brevican, a CNS-specific extracellular matrix protein is upregulated in glioma cells and its expression correl...
Article
A novel bioorthogonal gold nanoparticle (AuNP) template displaying interfacial nitrone functional groups for bioorthogonal interfacial strain-promoted alkyne–nitrone cycloaddition reactions has been synthesized. These nitrone–AuNPs were characterized in detail using ¹H nuclear magnetic resonance spectroscopy, transmission electron microscopy, therm...
Article
The Front Cover depicts the unique interaction between a tyrosine residue of our peptidomimetic and Arg283 in the binding pocket of the ghrelin receptor. This interaction is the rationale for the subnanomolar binding affinity of our ghrelin peptidomimetic and may be used to direct future SAR studies. The floating puzzle piece indicates the importan...
Article
The growth hormone secretagogue receptor type 1a (GHS‐R1a) is a Class A, rhodopsin‐like G Protein Coupled Receptor (GPCR) that is expressed in a variety of human tissues and is differentially expressed in benign and malignant prostate cancer. Previously the peptidomimetic [Lys5(4‐fluorobenzoyl‐4‐FB)]G7039 was designed as a molecular imaging tool fo...
Article
Three 4-amino-1,8-naphthalimide analogues were synthesized, consisting of the tridentate chelators di-2-picolylamine, (pyridin-2-ylmethyl)glycinate, and iminodiacetate conjugated to the naphthalimide scaffold. Coordination with fac-99mTc/Re(CO)3 resulted in metal complexes with overall charges of -1, 0, or +1. Upon coordination of Re(I), the initia...
Preprint
Proteinase Activated Receptor-4 (PAR4) is a member of the proteolytically-activated PAR family of G-Protein-coupled Receptors (GPCRs). PARs are activated following proteolytic cleavage of the receptor N-terminus by enzymes such as thrombin, trypsin, and cathepsin-G to reveal the receptor-activating motif termed the tethered ligand. The tethered lig...
Preprint
A bioorthogonal gold nanoparticle template displaying interfacial nitrone functional groups for bioorthogonal interfacial strain-promoted alkyne-nitrone cycloaddition (I-SPANC) reactions has been synthesized. The Nitrone-AuNPs were characterized in detail using <sup>1</sup>H NMR spectroscopy, TEM, TGA, and XPS and a nanoparticle raw formula was cal...
Article
PAR2 is a proteolytically activated G protein-coupled receptor (GPCR) that is implicated in various cancers and inflammatory diseases. Ligands with low nanomolar affinity for PAR2 have been developed, but there is a paucity of research on the development of PAR2-targeting imaging probes. Here, we report the development of seven novel PAR2-targeting...
Article
Full-text available
The stomach-derived hormone ghrelin mainly acts in the brain. Studies in mice have shown that the accessibility of ghrelin into the brain is limited and that it mainly takes place in some circumventricular organs, such as the median eminence. Notably, some known brain targets of ghrelin are distantly located from the circumventricular organs. Thus,...
Article
The enzyme enhancer of zeste homologue 2 (EZH2) plays a catalytic role in histone methylation (H3K27me3), one of the epigenetic modifications that is dysregulated in cancer. The development of a positron emission tomography (PET) imaging agent targeting EZH2 has the potential to provide a method of stratifying patients for epigenetic therapies. In...
Article
Full-text available
Currently, the early pre-clinical detection of left ventricular (LV) dysfunction is difficult as biomarkers are not specific for the cardiomyopathic process. The underlying molecular mechanisms leading to heart failure remain elusive, highlighting the need for identification of cardiac-specific markers. The growth hormone secretagogue receptor (GHS...
Article
The C-X-C chemokine receptor 4 (CXCR4) has been shown to be overexpressed in at least 23 types of cancer, including prostate cancer which has shown to have a significant distinction of expression rates between cancerous compared to healthy or benign tissue. In an attempt to exploit the difference in expression, we have synthesized a derivative of T...
Article
A chimeric drug design approach, merging the structure of an antagonist and an inverse agonist, results in a new molecular scaffold for targeting the ghrelin receptor (GHSR).
Article
High-grade gliomas are deadly cancers, and current standard-of-care has demonstrated limited success. The ability to specifically target glioma cells can allow for the development of safer and more efficacious brain cancer therapy strategies. Brevican, a CNS-specific extracellular matrix protein is upregulated in glioma cells and its expression cor...
Article
Full-text available
One-third of patients with heart disease develop heart failure, which is diagnosed through imaging and detection of circulating biomarkers. Imaging strategies reveal morphologic and functional changes but fall short of detecting molecular abnormalities that can lead to heart failure, and circulating biomarkers are not cardiac specific. Thus, there...
Article
ZnII concentrations in malignant prostate tissues are much lower than in benign or healthy, suggesting that ZnII levels are a potential biomarker for prostate cancer (PCa). Five 2,2′‐bipyridine ligands were synthesized containing amino substituents with varying electron‐donating ability for investigation as fluorescent ZnII indicators. The excited...
Article
The ghrelin receptor is a member of the growth hormone secretagogue receptor (GHS-R) family and is present at low concentrations in tissues such as the brain, kidney, cardiovascular system, and prostate. The ghrelin receptor plays an important role in cellular proliferation, apoptosis, invasion and migration associated with the progression of many...
Article
The receptor for hyaluronan mediated motility (RHAMM, gene name HMMR) belongs to a group of proteins that bind to hyaluronan (HA), a high-molecular weight anionic polysaccharide that has pro-angiogenic and inflammatory properties when fragmented. We propose to use a chemically synthesized, truncated version of the protein (706-767), 7 kDa RHAMM, as...
Article
The ghrelin receptor is a seven-transmembrane (7-TM) receptor known to have an increased level of expression in human carcinoma and heart failure. Recent work has focused on the synthesis of positron emission tomography (PET) probes designed to target and image this receptor for disease diagnosis and staging. However, these probes have been restric...
Preprint
Zn(II) concentrations in malignant prostate tissues are much lower than in benign or healthy, suggesting that Zn(II) levels are a potential biomarker for prostate cancer (PCa). Five 2,2'‐bipyridine ligands were synthesized containing amino substituents with varying electron donating ability for investigation as fluorescent Zn(II) indicators. The ex...
Preprint
Full-text available
Background: Currently, the early pre-clinical detection of left ventricular (LV) dysfunction is difficult as biomarkers are not specific for the cardiomyopathic process. The underlying molecular mechanisms leading to heart failure remain elusive, highlighting the need for identification of cardiac-specific markers. The growth hormone secretagogue r...
Article
New fluorescent dyes derivatized on a classical thiazole orange framework are able to show unexpectedly strong interaction signal and unusual binding selectivity with different structures of nucleic acid, particularly when bound with double-stranded DNA or G-quadruplex DNA. The present study reveals that these small binding ligands simply bearing a...
Article
A new fluorine‐containing azadibenzocyclooctyne (ADIBO‐F) has been designed using a synthetically accessible pathway. The fluorine‐18 prosthetic group was prepared from its tosylate precursor and isolated in 21‐35% radiochemical yield in 30 minutes. The ADIBO‐F has been incorporated into azide‐functionalized, cancer‐targeting peptides through a str...
Article
Fluorescently labelled ghrelin is an effective imaging probe for ex vivo biopsy analysis, in vivo distribution studies, and cell-based analyses. The objective of our study was to improve the receptor affinity and stability of this ghrelin probe through cyclization, thereby providing a chemical probe with advantages in specificity and sensitivity as...
Article
Hyaluronan is a simple extracellular matrix polysaccharide that actively regulates inflammation in tissue repair and disease processes. The native HA polymer, which is large (>500 kDa), contributes to the maintenance of homeostasis. In remodeling and diseased tissues, polymer size is strikingly polydisperse, ranging from <10 kDa to >500 kDa. In a d...
Article
Molecular imaging with PET (Positron Emission Tomography) is an attractive platform for non-invasive detection and assessment of disease. The development of a PET imaging agent targeting the ghrelin receptor (growth hormone secretagogue receptor type 1a or GHS-R1a) has the potential to lead to the detection and assessment of the higher than normal...
Article
Full-text available
Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), are present in cardiac tissue. Activation of GHSR1a by ghrelin promotes cardiomyocyte contractility and survival, and changes in myocardial GHSR1a and circulating ghrelin track with end-stage heart failure, leading to the hypothesis that GHSR1a is a biomarker for heart...
Article
Full-text available
Cancer targeting can be used for both tumor diagnosis and therapy. Recently, gold nanoparticles (AuNPs) have found utility in this field as they are very small in size, and thus display an enhanced permeability and retention effect, allowing them to be taken up by tumor cells through “passive targeting.” However, this accumulation is non-specific....
Article
High-grade gliomas are deadly cancers, and current standard-of-care has demonstrated limited success. The ability to specifically target glioma cells can allow for the development of safer and more efficacious brain cancer therapy strategies. Brevican (BCAN), a CNS-specific extracellular matrix protein is upregulated in glioma cells and its express...
Article
Full-text available
Angiogenesis is a dynamic process fundamental to the development of solid tumors. Epidermal growth factor-like domain 7 (EGFL7) is a protein whose expression is restricted to endothelial cells undergoing active remodeling that has emerged as a key mediator of this process. EGFL7 expression is associated with poor outcome in several cancers, making...
Article
The ghrelin receptor, also known as the growth hormone secretagogue receptor 1a (GHS-R1a), is a G-protein coupled receptor that is differentially expressed in healthy tissue and several cancers, including prostate, testicular, and ovarian. Selectively targeting the ghrelin receptor using fluorine-18 tagged entities would allow localization and visu...
Article
Thiazole orange (TO) stains most nucleic acids giving strong fluorescence signal non-specifically. To resolve the poor discriminating ability of TO among tertiary structures of DNAs, a planar and rotatable π–conjugated small molecule designed by replacing the methylene bridge with an ethylene bridge that slightly increases its structural flexibilit...
Presentation
Turnbull WL; Milne M; Luyt LG. A Bimodal 99mTc/Re-Labelled T140 Analogue for Evaluating CXCR4 Expression in Prostate Cancer. Oral Presentation, 22nd International Symposium on Radiopharmaceutical Sciences, Dresden, Germany, 2017, J. Labelled Cmpds. Radiopharm. 60, S83.
Article
Hyaluronan, CD44 and the Receptor for Hyaluronan-Mediated Motility (RHAMM, gene name HMMR) regulate stem cell differentiation including mesenchymal progenitor differentiation. Here, we show that CD44 expression is required for subcutaneous adipogenesis, whereas RHAMM expression suppresses this process. We designed RHAMM function blocking peptides t...
Article
The synthesis and characterization of emissive boron difluoride (BF2) complexes of 3-cyanoformazanate ligands produced using copper-assisted azide-alkyne cycloaddition (CuAAC) chemistry is described. Detailed spectroscopic and electrochemical characterization of benzyl-functionalized complexes served as models and demonstrated that triazole formati...
Article
Full-text available
High-grade gliomas are deadly cancers, and current standard-of-care has demonstrated limited success. The ability to specifically target glioma cells can allow for the development of improved theranostic agents leading to better detection methods and safer anti-cancer therapies. Brevican (BCAN), a CNS-specific extracellular matrix protein is upregu...
Conference Paper
High-grade gliomas are deadly cancers, and current standard-of-care has demonstrated limited success. The ability to specifically target glioma cells can allow for the development of improved theranostic agents leading to better detection methods, as well as safer anti-cancer therapies. Brevican (Bcan), a CNS-specific protein is upregulated in glio...
Article
The ghrelin receptor, also referred to as the growth hormone secretagogue receptor 1a (GHS-R1a), is a G protein-coupled receptor (GPCR) primarily expressed in the brain and pituitary. The wide spectrum of biological functions of GHS-R1a has rendered it a target for therapeutic drugs and for molecular imaging agents, for a variety of diseases. An im...
Article
Full-text available
Molecular targeting using ligands specific to disease markers has shown great promise for early detection and directed therapy. Bead-based combinatorial libraries have served as powerful tools for the discovery of novel targeting agents. Screening platforms employing magnetic capture have been used to achieve rapid and efficient identification of h...
Conference Paper
Full-text available
Alteration in genetic expression is as important as gene mutation in cancer development and proliferation. Epigenetic changes affect gene expression without altering the DNA sequence. Histone deacetylase (HDAC), an enzyme facilitating histone remodelling, can lead to silencing of tumor suppressor genes making HDAC inhibitors viable anticancer drugs...
Article
Covering: up to the end of 2015.Peptides are naturally occurring compounds that play an important role in all living systems and are responsible for a range of essential functions. Peptide receptors have been implicated in disease states such as oncology, metabolic disorders and cardiovascular disease. Therefore, natural peptides have been exploite...
Article
Full-text available
Accurate determination of urinary stone composition has significant bearing on understanding pathophysiology, choosing treatment modalities and preventing recurrence. A need exists for improved methods to determine stone composition. Urine of 31 patients with known renal calculi was examined with nanoscale flow cytometry and the calculi collected d...
Article
The universal fluorescent staining property of thiazole orange (TO) dye with most nucleic acids is regulated being specific for G-quadruplexes DNA structures distinctively by molecular modification to introduce a styrene-like substituent at ortho-position of TO scaffold. The investigation shows amazing outcomes because both experimental and molecul...
Chapter
Nanomedicine refers to the application of nanotechnology in medicine, and endeavors to diagnose, treat, and/or monitor disease on a nanoscale. Cancer nanotechnology is a quickly evolving field of interdisciplinary research that involves the biomedical application of nanoparticles, which are nanoscale devices that are able to overcome biological bar...
Conference Paper
Full-text available
High-grade gliomas are associated with very poor survival. Aggressive brain tumor cells invade into the surrounding normal brain and are impossible to remove by surgery. These cells are protected inside the brain from cancer drugs, leading inevitably to tumor regrowth and ultimately, patient death. There is an urgent need to develop therapeutics th...
Article
Full-text available
Fragments of the extracellular matrix component hyaluronan (HA) promote tissue inflammation, fibrosis and tumor progression. HA fragments act through HA receptors including CD44, LYVE1, TLR2, 4 and the receptor for hyaluronan mediated motility (RHAMM/HMMR). RHAMM is a multifunctional protein with both intracellular and extracellular roles in cell m...