Choline phosphate : an improved synthesis and applications in red cell and platelet
department or school: Science, Faculty of
department or school: Chemistry, Department of
data provider: DSpace
degree campus: UBCV
creator: Li, Youping
issued: 2019-04-23T16:19:40Z
issued: 2019
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Biomembrane adhesive materials that are effective in aqueous media have gained attention in the past decade owing to their broad uses such as tissue sealants and localized drug delivery agents. Here we demonstrate that hyperbranched polyglycerols (HPG) surface-modified with choline phosphate (CP) in a multivalent fashion are able to bind to eukaryotic cell membranes containing phosphatidyl choline (PC), which is structurally in a reverse orientation compared to CP. This work is dependent on a new synthesis of the CP reagent which allows an efficient production of HPG-CP. In the experimental design section, the preparation and characterization of a library of HPG molecules decorated with different densities of zwitterionic CP ligands is described. A post-polymerization pathway was followed that employs azido moieties on an HPG core for the conjugation of triple bond attached functional groups through “click” reaction, providing the desired HPG-CP macromolecule. The proportions of CP moieties were controlled by adjusting the monomer concentration. It was demonstrated that polymer conjugates carrying over 10% zwitterionic CP groups induced significant hemagglutination without causing red blood cell lysis or any cytotoxic effect. As the CP density was increased on the carrier HPG, cellular adhesion and aggregation became stronger as the intercellular contact area became maximized. The polymer conjugates, including HPG (20 kDa) decorated with 30 and 80 CP groups, were also found to be capable of activating platelets to a significant level while, interestingly, platelet aggregation tests demonstrated negative results. Future studies will investigate the mechanism of this unusual result, perhaps due to HPG-CP interacting with ADP which is intimately involved in platelet aggregation in vivo. DSC results showed that each CP ligand bound more than 37 water molecules on average, compared to each hydroxyl unit on the native HPG binding ~7, primarily owing to the dual-ion struct…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/69840
note: CHOLINE PHOSPHATE: AN IMPROVED SYNTHESIS AND APPLICATIONS IN RED CELL AND PLATELET BINDING by Youping Li B.Sc., McMaster University, 2016 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Chemistry) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2019 © Youping Li, 2019 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, a thesis/dissertation entitled: Choline phosphate: an improved synthesis and applications in red cell and platelet binding submitted by Youping Li in partial fulfillment of the requirements for The degree of Master of Science in Chemistry Examining Committee: Prof. Donald E Brooks, Chemistry and Pathology Supervisor Prof. Suzana K Straus, Chemistry Supervisory Committee Member Prof. Zachary Hudson, Chemistry Supervisory Committee Member Prof. Keith A R Mitchell, Chemistry Supervisory Committee Chair iii Abstract Biomembrane adhesive materials that are effective in aqueous media have gained attention in the past decade owing to their broad uses such as tissue sealants and localized drug delivery agents. Here we demonstrate that hyperbranched polyglycerols (HPG) surface-modified with choline phosphate (CP) in a multivalent fashion are able to bind to eukaryotic cell membranes containing phosphatidyl choline (PC), which is structurally in a reverse orientation compared to CP. This work is dependent on a new synthesis of the CP reagent which allows an efficient production of HPG-CP. In the experimental design section, the preparation and characterization of a library of HPG molecules decorated with different densities of zwitterionic CP ligands is described. A post-polymerization pathway was followed that employs azido moieties on an HPG core for the conjugation of triple bond attached functional groups through “click” reaction, providing the desired HPG-CP macro…
has type: Thesis/Dissertation
date issued: 2019-05
is shown at: 10.14288/1.0378377
language: eng
degree discipline: Chemistry
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/69840