Synthesis of Glycopeptides by Amidation of Aldoses with Peptides Using Iodine as the Oxidizing Agent
Date Issued
2008
Date
2008
Author(s)
Liu, Jia-Nan
Abstract
Carbohydrates play key roles in many biological processes and modulate the intrinsic properties of proteins. Glycoconjugates have become essential tools for investigation of many biological processes, and created new opportunities for the development of therapeutic and diagnostic strategies. In order to prepare glycoproteins, several conjugation methods have been developed for attaching carbohydrates to proteins. These methods lead to activated carbohydrate derivatives with a suitable functional group to be covalently linked to proteins. Some processes may be time-consuming and result in low overall yield because of many protection, coupling and deprotection steps. Though reductive amination is an extensive method for direct conjugation of unprotected and unmodified carbohydrate molecules, the process is sluggish. To find an improved conjugation method, our laboratory has developed a novel way to conjugate aldoses by amide-linkage with amine compounds via oxidative amidation using iodine as the appropriate oxidizing agent. In this thesis, the results of aldose amidation with representative α-amino esters and peptides are reported. The reaction occurred by condensation at the reducing end of carbohydrate molecules with amino group of the substrates. No racemerization at the α-carbon of α-amino esters, or cleavage of glycosidic bonds occurred under the reaction conditions. The desired product, aldonamide, was formed by nucleophilic attack of amine to the glyconolactone. The one-pot two-step process was convenient for aldose amidation with amino esters. Direct conjugation of disaccharide with poly-L-lysine and bovine serum albumin were also successfully carried out via oxidative amidation. The oxidative amidation may provide a new and rapid approach for direct synthesis of glycopeptides of unprotected and unmodified oligosaccharides by linkage with the amino groups of peptides. This method can be further applied to the preparation of carbohydrate-based vaccines and to increase bioavailability of peptide drugs.
Subjects
oxidative amidation
glycoepeptide
iodine
SDGs
Type
thesis
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