A 5-membered INOC cycloadduct 84 was employed to prepare alcohol 91, which was transformed into several cyclopent-2-enone derivatives 94-96. / By using intramolecular nitrile oxide-alkene cycloaddition (INOC) as the kep step to construct hydroxylated carbocycles, gabosine F was synthesized for the first time from L-arabinose. Hence, theoretically, gabosine B, which is the enantiomer of gabosine F, can also be synthesized from D-arabinose by the same synthetic strategy. / In this thesis, the background information on the construction of carbocycles from carbohydrates via intramolecular 1,3-dipolar cycloaddition is presented. A review regarding the syntheses of gabosine B and cocaine are also descibed. / Starting with D-ribose, INAC of nitrones 113, 129, and 140, bearing an alpha/beta-unsaturated ester as the dipolarophile was studied. The INAC endo-cycloadduct 141 (cycloheptane) was converted into natural cocaine sucessfully, together with cocaine analogues 162,169,170,173,175, and 177. / The regioselectivity of intramolecular nitrone-alkene cycloaddition (INAC) was studied. The INAC of hept-6-enose nitrone 98, with a 3,4- trans-pentylidene acetal as the only blocking group, afforded endo-cycloadduct 97 (cycloheptane) exclusively. This result concluded that the regiospecific outcome of this INAC reaction is due to the present of the 3,4-trans-pentylidene acetal blocking group. / To investigate the regioselectivity in INAC of hex-5-enose with a 2,3- trans-pentylidene acetal blocking group, nitrones 178 and 195 were prepared from D-mannitol. endo-Cycloadducts (cyclohexanes) were afforded exclusively. / So, King Ho. / Adviser: Kung Ming Tony Shing. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 165-171). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Leung Ling Yan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 218-259). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

This dissertation focuses on the synthesis and characterization of glyconanomaterials, as well as their applications in studying carbohydrate-protein interactions. A new and versatile method for coupling underivatized carbohydrates to nanomaterials including gold and silica nanoparticles was developed via the photochemically induced coupling reaction of perfluorophenylazide (PFPA). A wide range of carbohydrates including mono-, oligo- and poly-saccharides were conjugated to the nanoparticles with high yields and efficiency. New analytical methods were developed to determine the binding affinities of glyconanoparticles (GNPs) with lectins; these include fluorescence-based competition assay, dynamic light scattering (DLS) and isothermal titration calorimetry (ITC). Results showed that the multivalent presentation of carbohydrate ligands significantly enhanced the binding affinity of GNPs by several orders of magnitude compared to the free ligands. Systematic studies were carried out to investigate the impact of ligand presentation, i.e., the type and length of spacer linkage, the ligand density and the nanoparticle size on the binding affinity of the resulting glyconanoparticles. We used gold GNPs to study interactions with anti-HIV lectin cyanovirin-N (CV-N), and dye-doped silica nanoparticles for labeling glyans and developing high-throughput screening technique.

<p>Insulin as well as glucagon are important hormones in maintaining glucose homeostasis and regulating the metabolism in the body. Insulin receptors (IR) are transmembrane receptors that promote a signal transduction when activated by insulin. This can for example cause an increased influx of glucose into the cell performed by so called glucose transporters (GLUTs). These membrane proteins facilitate the transport of glucose from the blood into the cells, so the cell always has a constant supply of energy. Peroxisome proliferator-activated receptors (PPAR) are nuclear fatty acid receptors. They are activated by lipids and regulate fatty acid transcription. PPARδ/β is located in skeletal muscle and can promote fatty acid catabolism as well as cause a switch in fuel preference from glucose to fatty acids. It has been suggested that ligands for PPARδ could act as insulin sensitizers. The PPARγ coactivator-1α can increase mitochondrial content in skeletal muscle if over expressed. The same is true for endurance exercise.</p><p>Hormones released from adipose tissue can cause hyperphagia<strong> </strong>and obesity if over- or under expressed. They can also work in the opposite way by decreasing appetite with weight loss as an effect. Impaired signalling or dysfunctional receptor can cause insulin resistance, obesity and diabetes. Lipolysis occurs in adipose tissues and is conducted by three enzymes, namely adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoglyceride lipase (MGL). There are some factors that can increase lipolysis such as caffeine, a low glycemic index, high protein intake and training.</p><p>The enzyme PEPCK is involved in the gluconeogensis in the liver and kidney cortex, and also in the glyceroneogenesis in the liver, as well as in brown and white adipose tissue. When overexpressed in skeletal muscle the enzyme increases the muscle activity. The overexpression of the enzyme did promote the β-oxidation as energy source for the muscles during exercise, instead of muscle glycogen as fuel.</p><p>The processes of protein synthesis and breakdown are together called protein turnover. Muscle grows when synthesis is greater than breakdown, and withers if breakdown exceeds the level of synthesis. Acute effects of training is catabolic, but long time exercise causes however an increased protein synthesis. Leucine, an essential amino acid, has an important role in the initiation phase of translation. Glutamine is probably important in the regulation of muscle protein synthesis and breakdown. Together with glutamate, aspartate and asparagine, these are responsible for the amino acid metabolism that occurs in the muscles. Protein synthesis reaches its maximum in the recovery phase after intense training.</p>

Insulin as well as glucagon are important hormones in maintaining glucose homeostasis and regulating the metabolism in the body. Insulin receptors (IR) are transmembrane receptors that promote a signal transduction when activated by insulin. This can for example cause an increased influx of glucose into the cell performed by so called glucose transporters (GLUTs). These membrane proteins facilitate the transport of glucose from the blood into the cells, so the cell always has a constant supply of energy. Peroxisome proliferator-activated receptors (PPAR) are nuclear fatty acid receptors. They are activated by lipids and regulate fatty acid transcription. PPARδ/β is located in skeletal muscle and can promote fatty acid catabolism as well as cause a switch in fuel preference from glucose to fatty acids. It has been suggested that ligands for PPARδ could act as insulin sensitizers. The PPARγ coactivator-1α can increase mitochondrial content in skeletal muscle if over expressed. The same is true for endurance exercise. Hormones released from adipose tissue can cause hyperphagia and obesity if over- or under expressed. They can also work in the opposite way by decreasing appetite with weight loss as an effect. Impaired signalling or dysfunctional receptor can cause insulin resistance, obesity and diabetes. Lipolysis occurs in adipose tissues and is conducted by three enzymes, namely adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoglyceride lipase (MGL). There are some factors that can increase lipolysis such as caffeine, a low glycemic index, high protein intake and training. The enzyme PEPCK is involved in the gluconeogensis in the liver and kidney cortex, and also in the glyceroneogenesis in the liver, as well as in brown and white adipose tissue. When overexpressed in skeletal muscle the enzyme increases the muscle activity. The overexpression of the enzyme did promote the β-oxidation as energy source for the muscles during exercise, instead of muscle glycogen as fuel. The processes of protein synthesis and breakdown are together called protein turnover. Muscle grows when synthesis is greater than breakdown, and withers if breakdown exceeds the level of synthesis. Acute effects of training is catabolic, but long time exercise causes however an increased protein synthesis. Leucine, an essential amino acid, has an important role in the initiation phase of translation. Glutamine is probably important in the regulation of muscle protein synthesis and breakdown. Together with glutamate, aspartate and asparagine, these are responsible for the amino acid metabolism that occurs in the muscles. Protein synthesis reaches its maximum in the recovery phase after intense training.

Inhibiting the formation of ice is an essential process commercially, industrially, and medically. Compounds that work to stop the formation of ice have historically possessed drawbacks such as toxicity or prohibitively high active concentrations. One class of molecules, ice recrystallization inhibitors, work to reduce the damage caused by the combination of small ice crystals into larger ones. Recent advances made by the Ben lab have identified small molecule carbohydrate analogues that are highly active in the field of ice recrystallization and have potential in the cryopreservation of living tissue. A similar class of molecules, kinetic hydrate inhibitors, work to prevent the formation of another type of ice – gas hydrate. Gas hydrates are formed by the encapsulation of a molecule of a hydrocarbon inside a growing ice crystal. These compounds become problematic in high pressure and low temperature areas where methane is present - such as an oil pipeline. A recent study has highlighted the effects of antifreeze glycoprotein, a biological ice recrystallization inhibitor, in the inhibition of methane clathrates. Connecting these two fields through the synthesis and testing of small molecule ice recrystallization inhibitors in the inhibition of methane hydrates is unprecedented and may lead to a novel class of compounds.

ABSTRACT Carbohydrates in various forms play vital roles in numerous critical biological processes including cell-cell adhesion and communication, embryo development, immune response, etc. Fluorescent sensors for such carbohydrates have a wide range of potential applications including glucose concentration determination, cell labeling and targeting based on carbohydrate biomarkers, as in vitro diagnostic tools, and biomarker-directed cellular imaging. Our group has been interested in the design and synthesis of multi-boronic acid compounds with well-defined three-dimensional scaffolding for the specific recognition of selected carbohydrate biomarkers. Aberrant expression of carbohydrate antigens such as sialyl Lewis X (sLex), sialyl Lewis A (sLea), Lewis X (Lex), and Lewis Y (Ley) have been associated with tumor formation and metastasis in various cancer types.1-4 As such, for our initial design, we have selected sialyl Lewis X (sLex) as our potential target due to implication in the development of liver and colon cancer.5, 6 Herein, we describe the design, synthesis and evaluation of four such compounds, each having about ten linear steps in its synthesis. In addition to the design of fluorescent probes for cell surface carbohydrates, we also have designed lipophilic boronic acid derivatives as potential fusogenic agents. Due to boronic acid¡¯s ability to bind to 1,2 and 1,3 cis diols, we hypothesize that the aliphatic chain should be able to insert into lipid cellular membrane and the boronic acid units should allow for the ¡°attachment to neighboring cells¡± through complexation with cell surface glycans. Such interactions should allow the boronic acid compounds to bring two or more cells together for fusion. Herein, we have described the methodologies of the design of such compounds. INDEX WORDS: Boronic acid, sialyl Lewis X probe, boronolectin, fluorescence, sensor, cell-cell fusion, fusogen, immunotherapy.

Research investigating the effects of pre-exercise meals with varying glycemic indices on exercise performance in intermittent sports is scarce. This study determined whether whole foods of low glycemic index (GI) resulted in a metabolic and performance advantage, in comparison to high GI foods, when eaten prior to extended intermittent cardiovascular exercise, such as tournament soccer play. Consenting trained participants (10 males, 4 females, 25.8 ± 7.3 y) completed two simulated soccer tournaments separated by at least seven days. Each testing day included two 90-minute soccer matches separated by a three hour break. Using a randomized cross-over design, low-GI, lentil-based meals (GI~42) or high-GI, potato-based meals (GI~78) matched for caloric value were consumed two hours prior to and then within one hour after the first soccer match. Blood glucose, lactate, insulin, free fatty acids, and respiratory gases were measured throughout the post-prandial and testing periods. Ratings of perceived exertion (RPE) and gastrointestinal symptoms were also recorded. Performance was measured by the distance covered during five one-minute sprints, separated by two minute and thirty second rest intervals, at the end of each match. Peak post-prandial blood glucose was higher (p<0.05) in the high-GI trial (8.9 ± 2.2 molL-1 [SD]) compared to the low GI trial (5.9 ± 1.3 mmolL-1) as was insulin prior to the start of exercise (19.4 ± 2.0 versus 9.2 ¬± 1.3 umolL-1, p<0.05). Blood lactate levels were significantly higher (p<0.05) at the end of the second match during the high-GI trial (6.1 ± 1.2 mmolL-1) compared to the low-GI trial (2.5 ± 0.4 mmolL-1). Breath-by-breath analysis showed lower (p<0.05) carbohydrate oxidation during the low-GI trials compared to the high-GI at the start of the first soccer match (p<0.05). Subjects reported greater feelings of hunger during the high-GI trial versus greater feelings of fullness during the low-GI trial (p<0.05), but RPE during the low-GI (14.1 ± 0.3) was similar to the high-GI meal (14.2 ± 0.3). Sprint distance was not significantly different between treatments (p=0.27). Overall, these findings suggest that lentil-based, low-GI foods are a comparable alternative to traditional high-GI pre-exercise meals, as they result in similar performance outcomes but improved metabolic profiles. Over the long-term, improving metabolic conditions during exercise may be beneficial to the health of athletes.

Research investigating the effects of pre-exercise meals with varying glycemic indices on exercise performance in intermittent sports is scarce. This study determined whether whole foods of low glycemic index (GI) resulted in a metabolic and performance advantage, in comparison to high GI foods, when eaten prior to extended intermittent cardiovascular exercise, such as tournament soccer play. Consenting trained participants (10 males, 4 females, 25.8 ± 7.3 y) completed two simulated soccer tournaments separated by at least seven days. Each testing day included two 90-minute soccer matches separated by a three hour break. Using a randomized cross-over design, low-GI, lentil-based meals (GI~42) or high-GI, potato-based meals (GI~78) matched for caloric value were consumed two hours prior to and then within one hour after the first soccer match. Blood glucose, lactate, insulin, free fatty acids, and respiratory gases were measured throughout the post-prandial and testing periods. Ratings of perceived exertion (RPE) and gastrointestinal symptoms were also recorded. Performance was measured by the distance covered during five one-minute sprints, separated by two minute and thirty second rest intervals, at the end of each match. Peak post-prandial blood glucose was higher (p<0.05) in the high-GI trial (8.9 ± 2.2 molL-1 [SD]) compared to the low GI trial (5.9 ± 1.3 mmolL-1) as was insulin prior to the start of exercise (19.4 ± 2.0 versus 9.2 ¬± 1.3 umolL-1, p<0.05). Blood lactate levels were significantly higher (p<0.05) at the end of the second match during the high-GI trial (6.1 ± 1.2 mmolL-1) compared to the low-GI trial (2.5 ± 0.4 mmolL-1). Breath-by-breath analysis showed lower (p<0.05) carbohydrate oxidation during the low-GI trials compared to the high-GI at the start of the first soccer match (p<0.05). Subjects reported greater feelings of hunger during the high-GI trial versus greater feelings of fullness during the low-GI trial (p<0.05), but RPE during the low-GI (14.1 ± 0.3) was similar to the high-GI meal (14.2 ± 0.3). Sprint distance was not significantly different between treatments (p=0.27). Overall, these findings suggest that lentil-based, low-GI foods are a comparable alternative to traditional high-GI pre-exercise meals, as they result in similar performance outcomes but improved metabolic profiles. Over the long-term, improving metabolic conditions during exercise may be beneficial to the health of athletes.

No description available.