Sulfation of tyrosine residues is a post-translational modification that occurs on many secretory as well as transmembrane proteins. This modification is believed to be essential for numerous biological processes. However, one of the factors hindering the study of the significance of sulfotyrosine (sTyr) within a protein is the absence of a general method that enables the synthesis of sTyr peptides in satisfactory yields and purity. A general approach to the synthesis of sTyr-bearing peptides was developed in which the sTyr residue is incorporated into the peptides with the sulfate group protected. For the implementation of this general approach a new protecting group for sulfates, namely, the dichlorovinyl (DCV) group was developed. This was accomplished by conducting a careful analysis of the reaction of a trichloroethyl (TCE)-protected sulfate ester with piperidine and 2-methylpiperidine (2-MP). A unique sulfuryl imidazolium reagent, compound 2.22, was also developed that enabled the ready synthesis of DCV-protected sulfates. This reagent was used to prepare the amino acid building block FmocTyr(SO3DCV)OH (2.23). An alternative and more economical synthesis of FmocTyr(SO3DCV)OH (2.23) was also developed that did not require reagent 2.22. Fmoc-based solid phase peptide synthesis (SPPS) was used to incorporate 2.23 into peptides using 2-MP for Fmoc removal. After cleavage of the peptide from the support, the DCV group was removed by hydrogenolysis to give sTyr peptides in good yield and purity. Using this approach a variety of sTyr peptides were prepared including a tetrasulfated 20-mer corresponding to residues 14-33 in chemokine receptor D6 and a disulfated 35-mer corresponding to residues 8-42 of the N-terminus region of the chemokine receptor DARC and this is the largest multisulfated sTyr–bearing peptide made to date. It was also demonstrated that the incorporation of an important non-hydrolyzable sTyr analog, 4-(sulfonomethyl)phenylalanine (Smp), into peptides can be accomplished in good yield by protecting the sulfonate residue with a TCE group during SPPS. This approach was shown to be superior to the previously reported method where the sulfonate group is unprotected. Finally, a number of sulfotyrosine bearing peptides were synthesized and tested as protein tyrosine phosphatase-1B (PTP1B) inhibitors

none

Bottom water hypoxia and its influence on the environment have been topics of increasing concern for many coastal regions. This research addresses both spatial and temporal variability in sediment biogeochemistry at the southeastern region of Corpus Christi Bay, TX, where seasonal (summer) hypoxia occurs. Traditional techniques for determination of a variety of dissolved and solid components, benthic oxygen demand, and sulfate reduction rates were augmented by measurements using solid state microelectrodes to simultaneously determine concentrations of dissolved O2, Mn2+, Fe2+, and [sigma]H2S in multiple small - interval (1 mm) depth profiles of sediment microcosms. Oxygen concentrations in the overlying water were manipulated in the sediment microcosms and electrode depth profile measurements were made over ~ 500 hours of experimentation. Laboratory and field microelectrode results were in good agreement for both norm - oxic and anoxic time periods. Results indicated that iron (Fe2+) and sulfide ([sigma]H2S) were the redox reactive species in these sediments. During hypoxic conditions an upward migration of dissolved Fe2+and [sigma]H2S through the sediment column and, at times, into the overlying water was observed as the dissolved oxygen concentrations decreased. A corresponding decline in the vertical extent of these redox species occurred when the overlying water was re-oxidized. When both dissolved iron and sulfide coexisted, FeS minerals were formed in the sediment, preventing sulfide diffusion into the overlying water. However, after a long duration of hypoxia (> 200 hours) this buffering capacity was exceeded and both iron and sulfide penetrated into the overlying waters. Results indicated that iron may have a greater influence on hypoxia than sulfide because its concentration in the overlying waters during induced hypoxia was an order of magnitude greater than those of sulfide. Moreover, in the southeastern region of the Bay, where mixing was minimal and the water column was shallow, the sediments alone may have caused the onset of the hypoxic event in a relatively short time period (< 5.5 days). These results demonstrated that in shallow marine environments where seasonal hypoxia occurs, such as Corpus Christi Bay, the associated major changes that take place in the sediment biogeochemistry must be included in benthic - pelagic models for overlying water hypoxia.

This study was conducted to study absorption of glucosamine and chondroitin sulfate and to measure any changes in blood concentration of these compounds following feeding them to horses in different amounts. Six mature mares were used in a replicated 3x3 Latin square designed experiment. The experiment consisted of three 15-day periods, which included 10 days of diet adaptation followed by a 5-day sampling period. Blood was drawn on one day during each sampling period. Horses were fed a control diet (40% hay, 60% concentrate) balanced to meet NRC (1989) requirements for maintenance of mature horses. In one experimental diet, 2.0 g chondroitin sulfate and 5.5 g glucosamine were added to the basal ration at each feeding. In the other experimental diet, 3.5 g chondroitin sulfate and 8.5 g glucosamine were added to the basal ration at each feeding. Following total collections, blood was centrifuged and plasma was harvested and data analyzed for the presence of each compound. Analyses for plasma glucosamine were performed in the Protein and Chemistry Lab at Texas A&M University using HPLC. Chondroitin sulfate in the plasma was analyzed using a color reagent, dimethylmethylene blue, followed by UV spectrophotometry. There were no significant differences (P<0.05) in the concentration of chondroitin sulfate or glucosamine concentrations in plasma when comparing the three different diets. This leads to a conclusion that these compounds were not absorbed through the intestinal wall into the bloodstream in the same form as they were fed. This poses a question as to whether or not oral forms of these compounds are absorbed and are able to migrate to joints through the blood to improve joint function. With the significant economic impact that products containing chondroitin sulfate and glucosamine are making in the animal nutrition industry, more research is needed to further elucidate actual efficacy of these compounds in diet supplements for horses.

Thesis (Ph. D.)--University of Pittsburgh, 1915. / Vita.

Thesis (doctoral)--Helsinki University of Technology, 2000. / Includes bibliographical references. Also available on the World Wide Web.

Thesis (Ph. D.)--Lehigh University, 2000. / Includes vita. Includes bibliographical references (leaves 170-174).

Reproduction de : Thèse doctorat : Biologie et physiologie végétales : Reims : 2007. / Titre provenant de l'écran titre. Bibliogr. p. 106-139.

Reproduction de : Thèse d'exercice : Médecine vétérinaire : Toulouse 3 : 2008. / Titre provenant de l'écran titre. Bibliogr. p. 121-142.

Thesis (M.S.) in Chemical Engineering--University of Maine, 2002. / Includes vita. Includes bibliographical references (leaves 80-83).