Master of Science / Department of Grain Science and Industry / X. Susan Sun / Soybean protein modified with sodium bisulfite behaves like latex adhesives, with adhesive strength comparable to formaldehyde-based adhesives. β-conglycinin and glycinin are two major protein components of the adhesive system. The objective of this research was to investigate the effect of sodium bisulfite on the physicochemical, morphological, and adhesion properties of glycinin and β-conglycinin in order to better understand the function of glycinin and β-conglycinin in the formation of the soy latex adhesive. Sodium bisulfite broke the disulfide bonds that linked acidic and basic polypeptides of glycinin, and the reducing effect was enhanced with increasing sodium bisulfite concentration. Although cleavage of disulfide bonds was expected to destabilize proteins, the thermal stability of glycinin increased as the sodium bisulfite concentration increased. Sodium bisulfite modified glycinin had higher surface hydrophobicity, which facilitated hydrophobic interations between molecules and aggregation of glycinin. The balance between hydrophobic interactions and electrostatic forces makes glycinin form unique chain-like structures. Adhesive performance of glycinin dropped significantly at lower sodium bisulfite concentration and then increased as sodium bisulfite concentration increased up to 24 g/L. Excess sodium bisulfite was detrimental to adhesive strength and water resistance. High-molecular-weight aggregates were observed in unmodified β-conglycinin, but these aggregates were dissociated by sodium bisulfite treatment. Similar to glycinin, the thermal stability of β-conglycinin was improved by the modification. However, the denaturation enthalpy of β-conglycinin decreased significantly at high level of sodium bisulfite (36 g/L). The turbidity at pH 4.8 also dropped extensively at the concentration of 36 g/L. The contact angle of β-conglycinin reached its minimum at 6 g/L sodium bisulfite on cherry wood and 24 g/L on glass. Morphology study proved that sodium bisulfite modification made the β-conglycinin solution more dispersed. At pH 9.5, water resistance of β-conglycinin was improved to a small extent by 6 g/L sodium bisulfite. At pH 4.8, adhesive performance was enhanced by 3 g/L and 6 g/L sodium bisulfite. High level of sodium bisulfite at 36 g/L reduced the adhesive performance of β-conglycinin drastically.

<p> The objective of this study was to synthesize and biologically evaluate a series of novel nucleoside derivatives of the naturally occurring lignans, podophyllotoxin and 4'-demethylepipodophyllotoxin. Epipodophyllotoxin derivatives display two types of biological activity: while the naturally occurring compounds are potent inhibitors of microtubule polymerization, two semi-synthetic glycoside derivatives, viz VP16-213 (etoposide) and VM26 (teniposide), are specific inhibitors of mammalian DNA topoisomerase II. The latter two compounds have proven to be very useful in the treatment of many different types of cancer. In this study, the glycoside moiety of VP16-213/VM26 was replaced with either a thymidine or a 2'-deoxyadenosine group. The synthetic approach involved protective group chemistry, where functional groups on the nucleosides and DMEP were selectively blocked prior to their condensation in the presence of boron trifluoride etherate catalyst. These compounds are of interest because they involve substitution of the glucoside moiety with a nucleoside residue, whose effect on the biological activity of epipodophyllotoxin derivatives has not been examined. The biological activity of these compounds was assessed by examining their cross-resistance patterns towards a set of Chinese hamster ovary mutants resistant to podophyllotoxin VP16-213/VM26, mitotic index, and by a competition assay. From the cross resistance assay, all of the thymidine derivatives were found to be considerably less active than the parent podophyllotoxin and 4'-demethylepipodophyllotoxin molecules, while the 2'-deoxyadenosine derivatives were found to be completely inactive. The cross-resistance patterns of the thymidine derivatives suggests that these compounds display podophyllotoxin-like activity in vivo and show no VP16-213/VM26-like activity. Treatment of wild type cells with the active thymidine derivatives (compounds 1.2, 2.2, 2.3, and 2.4) increased the mitotic indices approximately ten-fold in a dose-dependent manner, which parallels the results of the dose-response curves in the initial cross-resistance assay. Furthermore, there was a marked increase in the levels of drug required to elevate the mitotic index in second-step mutants resistant to podophyllotoxin, again lending support to the initial results indicating that the cellular target of these compounds is tubulin. Only one compound (1.2), was found to out compete the binding of radiolabelled podophyllotoxin to purified calf brain tubulin. However, due to their low activity relative to podophyllotoxin, most of these compounds were insoluble at concentrations required to out compete the binding of radiolabelled podophyllotoxin. Molecular modelling studies have provided useful insights regarding the structure/activity relationships among the active and inactive nucleoside derivatives showing podophyllotoxin-like antimitotic activity. There appears to be steric limits for substituents attached at the C4 moiety that maintain the antimitotic activities of the parent molecules. The electrostatic potential and hydrophobic properties of these groups also seem to play a role in the degree of activity these compounds show, but remain unclear at this point. By simple comparison of the three-dimensional structures of these compounds there appears to be a very limited spacial and electrostatic requirement for the bulky glycosidic moiety attached to C4 which is essential for targeting VP16-213 and VM26 to DNA topoisomerase II. Thus, several important structural features which may distinguish the selectivity POD derivatives show for either tubulin or DNA topoisomerase II are described.</p> / Thesis / Master of Science (MSc)