Rational design and synthesis of sialyl Lewis X mimetics and other glycomimetics.
Item
-
Title
-
Rational design and synthesis of sialyl Lewis X mimetics and other glycomimetics.
-
Identifier
-
AAI3024773
-
identifier
-
3024773
-
Creator
-
Cheng, Xuhong.
-
Contributor
-
Adviser: David R. Mootoo
-
Date
-
2001
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Chemistry, Organic
-
Abstract
-
Sialyl Lewis X (sLex) is a tetrasaccharide expressed on the surface of neutrophils and tumor cells. It was identified to be the smallest recognizable ligand for selectins. The interaction between sLex and selectins initializes the inflammatory cascade for recruitment of leukocytes to a site of tissue damage, which causes the inflammatory diseases. Related adhesion is involved in metastasis. A large number of sLex mimetics have been developed as biological probes or potential therapeutics. An 1,1-Gal-Man disaccharide which emerged from Wong's group was reported to be more active than sLex in binding to E- and P-selectin.;In this thesis the synthesis of the C-, carba- and aza-C-disaccharide analogues of the molecule is reported. These natural structures are topographically similar to the parent O-saccharide and are of special interest because of their stability to enzymatic and chemical hydrolysis. The methodology used for the synthesis of the target compounds involved the use of 1-thio-1,2-O-isopropylidene acetals (TIA's) as precursors. A key reaction is the oxocarbenium ion-enol ether cyclization to form a cyclic enol ether. This chemistry was also applied to glycomimetics of glycosyinositols and other important disaccharides. The conformational and selectin binding properties of the O- and C-glycoside analogues of the aforementioned sLex mimetics, as well as two novel galactoside analogues for the gp-120 binding affinity are reported.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
