Theses and Dissertations from UMD

Permanent URI for this communityhttp://hdl.handle.net/1903/2

New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

Browse

Filters

2004 - 200912010 - 20201

Settings

Subject: search.filters.subject.glycosylation

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    CHEMOENZYMATIC MODULATION OF GLYCOPEPTIDE ANTIGENS AS TARGETS FOR HIV VACCINE DISCOVERY AND LIVER CANCER DIAGNOSIS
    (2020) Zhang, Roushu; Wang, Lai-Xi; Biochemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Glycosylation is a critical post-translational modification of proteins. Viral pathogens use the host glycosylation machinery to facilitate their entry and hide them from the host immune recognition. Moreover, changing the glycosylation pattern is often related to the development of diseases, such as the emergence of carcinomas. Therefore, carbohydrates are attractive targets for various infectious diseases and pathogenic disorders. Nonetheless, as the synthesis of glycans is not template-driven, glycoforms obtained from natural resources are heterogeneous. We address this issue by employing glycosidase inhibitors to modulate protein glycosylation during expression, and also by chemoenzymatic glycan remodeling of glycopeptide antigens. Three projects related to this topic are described herein.In the first project, a series of glycan-defined HIV-gp120-derived glycoprotein immunogens were expressed and engineered. We successfully demonstrated the glycan-dependency of a variety of HIV-targeting broadly neutralizing antibodies (bnAbs). Our immunogens bearing the high-mannose glycosylation have adequate antigenicity towards the bnAbs evaluated, rendering these immunogens promising vaccine candidates for HIV/AIDS. The second project focused on designing novel glycopeptide immunogens for raising glycan-specific antibodies to detect the early stage of liver cancer. Here we chose the fucosylated alpha-fetoprotein as our target since it is related to the development of liver cancer. There is no available antibody specifically recognizing this glycoform and therefore it is still challenging to utilize this parameter to evaluate the condition of patients. We chemoenzymatically synthesized alpha-fetoprotein-derived glycopeptides with core-fucosylation and subjected these immunogens to animal studies. The antisera displayed glycan-dependent IgG responses, laying a foundation to develop monoclonal antibodies that target the fucosylated alpha-fetoprotein. The discovery of such antibodies will be valuable to sensitively diagnose liver cancer in clinics. Lastly, developing enzyme tools is equally important to harness the field. In the final project of my dissertation, we revisited the substrate preference of the human α(1-6) fucosyltransferase. The enzyme exhibited a relaxed substrate preference when a proper glycoprotein, glycopeptide, or an Fmoc modification is attached to the acceptor substrates. This discovery provides new insights into studying glycosyltransferases and offers new approaches to chemoenzymatically synthesizing core-fucosylated glycoproteins and glycopeptides. Together, the studies present new avenues for studying glycan-related biological processes and diseases.
  • Thumbnail Image
    Item
    Absorption, Excretion, and Transformation of Individual Anthocyanins in Rats
    (2004-08-06) He, Jian; Giusti, Monica M; Magnuson, Bernadene A; Food Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Anthocyanins are polyphenolics responsible for most red to purple colors in plants. Human consumption is increasing because of their potential health benefits and use as natural colorants. However, their absorption and metabolism are not well characterized. We compared anthocyanin absorption and excretion in rats receiving chokeberry, bilberry or grape enriched diet (4g anthocyanin/kg) for 13 weeks. Traces of anthocyanins and metabolites were detected in plasma. In urine, intact anthocyanins and methylated derivatives (~ 24, 8, 15 mg cy-3-gla equivalent/L urine for chokeberry, bilberry, grape) were found. High metabolite concentration suggested accumulation of methylated anthocyanins in tissue. Fecal anthocyanin extraction was maximized with aqueous methanol (60%). Anthocyanin concentration in feces ranged from 0.7 to 2g anthocyanin/kg, similar to cecal content. In the gut, anthocyanin degradation was high for glucosides, moderate for galactosides and negligible for arabinosides and xylosides. Both, glycosylation and acylation seemed to affect the bioavailability of anthocyanins in vivo.