Morris, MorganMorganMorris2025-11-192025-11-192023 the A2023http://hdl.handle.net/10197/30220Herein, we present the rational design and synthesis of a series of (poly)ethylene glycol lactose-drug conjugates with suitable spatial geometries and solubility profiles to facilitate endocytosis by the asialoglycoprotein receptor (ASGP-R). This receptor has been recognised as a promising vector for targeted drug delivery due to its sole expression on liver cells. Chapter 1 discusses the biological function and structure of the asialoglycoprotein receptor. Emphasis is given to the chronological development of literature in this research area and the development of suitable targeting scaffolds. Chapter 2 explores the rational design of an ASGP-R targeting platform using the disaccharide lactose, as well as exploring the choice of branching unit and considerations around internalisation. Focus is given to the site-selective conjugation strategies in the use of fluorescein as an internalisation probe. Chapter 3 explores specific applications of ASGP-R targeting for hepatocellular carcinoma using the anticancer drug camptothecin. Attention is given to features of glycoconjugate design and structure-activity relationships. Chapter 4 details a synthetic methodology for the fluorination of piperidine scaffolds and a rational investigation of conformational preference based upon NMR spectroscopic analysis and crystallographic data.enLactoseFluoresceinCamptothecinFluoropiperidineDoctoral Thesishttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/