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Biomemitic Glycomacromolecules for Medical Applications

by Zhang, Yalong

Abstract (Summary)
Glycoproteins and glycoceramides are fundamental to many important biological processes including fertilization, immune defense, viral replication, parasitic infection, cell growth, cell-cell adhesion, degradation of blood clots and inflammation. Although the specific functions of glycan are still under study, but two major functions are quite clear. One function is to serve as recognition markers, and the other is to stabilize proteins. Here, five glycomacromolecules have been designed and prepared for medical applications by mimicing glycoproteins. And three 3€™-N substituted galceramide have been synthesized for structure activity relationship research against tumor. In chapter 2, a lacotose glycosylated bovine hemoglobin (Hb) has been prepared as blood substitute for hemorrhagic shock to delivery oxygen to low pO2 tissues and organs by selectively conjugating a lactose derivative to Cys-93 on the ? chain of bovine Hb. Chapter 3 describes the preparation of a bifunctional linker. One end is to directly conjugate the free reducing end of oligosaccharides by forming a stable oxime. The other end contains maleimide group for linking Cys on proteins. In Chapter 4, a glycohydrogel containing sugar blood B epitols has been prepared as an anti-adhesion agent against norovirus. The strong inhibition and the biocompatibility of the hydrogel suggest that the glycosylated hydrogel holds potential to be used as a prophylactic antinorovirus drug. In Chapter 5, Shiga toxins (Stxs) producing E. coli (STEC) has been detected by Gal-?1,4-Gal glycopolydiacetylene (GPDA) nanoparticles through the colorimetric change triggered by the recognition between carbohydrates and Stxs. This method provides a highly selective, rapid, sensitive and quantitative approach for routine checks of STEC. In Chapter 6, N-isopropyl acrylamide (NIPAm) based copolymers, polyNIPAm-NAS and polyNIPAm-NAS-Sty (styrene), have been prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization method. The copolymers are glycosylated by Pk trisaccharides derivatives and it is found that the second generation glycopolymer, polyNIPAm-Pk-Sty, can self-assemble into GNPs at physiological temperatures. In Chapter 7, pH-sensitive Pk GNPs have been developed to delivery tacrolimus. No release is observed at pH 4.7 and 20 % of the drug is released at pH 7.5. Three 3€™-N substituted a-galceramide have been de nova synthesized in 24 steps and described in Chapter 8 for studying the structure activity relationship of ?-galactosylceramide (?-GalCer) against tumors.
Bibliographical Information:

Advisor:

School:The Ohio State University

School Location:USA - Ohio

Source Type:Master's Thesis

Keywords:glycomacromolecules biomemitic glyconanoparticles glycohydrogel

ISBN:

Date of Publication:01/01/2008

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