I. Study of protein-carbohydrate interaction on carbohydrate arrays. II: Synthesis of analogues of sphingosine base, nitric oxide donors and HDAC inhibitors

This dissertation describes my Ph.D. work that focused on the synthesis of thiol linker containing carbohydrate conjugates, synthesis of thiol difunctional linkers for the preparation of carbohydrate arrays to study protein carbohydrate interaction and the synthesis of analogues of sphingosine base, novel nitric oxide donors, HDAC inhibitors.;In chapter 1, carbohydrate array was introduced and the development of carbohydrate technology was reviewed.;In chapter 2, three thiol linker containing carbohydrate conjugates, mannose thiol linker conjugate, alkanethiol containing glycopolymer and lactose thiol linker conjugate, were synthesized and used to study protein carbohydrate interaction. Carbohydrate arrays from mannose thiol linker were used to detect the bacterial adhesion, arrays from glycopolymer conjugated with mannose and alkanethiol linker were used to detect lectin binding and the assay of enzymatic synthesis of alpha-1, 3 galactosyl trisaccharide was performed on the lactose array.;In chapter 3, two thiol difunctional linkers with methoxyamino or aminooxy functionality were synthesized as the substrates of functional self-assembled monolayers which will be further derivatized for the formation of carbohydrate arrays.;In chapter 4, using amino acid L-serine as the starting material, analogues of sphingosine base were synthesized for the study of biological role of glycolipids.;In chapter 5, a series of N-alkyl N'-hydroxyguanidines were synthesized and demonstrated to act as substrates of nitric oxide synthases (NOS). The discovery of these non-amino acid hydroxyguanidines as novel substrates also led to the discovery of a novel-binding mode of NOS.;In chapter 6, a series of SAHA analogues modified on the moiety of hydroxamic acid were synthesized to probe the structure requirement for the HDAC inhibitors.