The synthesis of galectin-3-targeted cancer imaging agents

[摘要] Galectin-3 is an animal lectin that recognises and binds to β-galactosides in glycoconjugates and is frequently over-expressed in cancerous states, potentially allowing inhibitors to serve as vector tags for targeted image contrast agents to give enhanced MRI and flourescence images. Derivatives of lactosamine with 3'-arylamides have been shown to be excellent inhibitors of galectin-3: 3'-naphthamide derivatives of lactosamine have previously been shown to bind to galectin-3 with k\(_d\)<1 μM, and form the basis of the target imaging agent, which will also incorporate a spacer unit and a probe molecule. Problems with the reduction/acylation of an azide in a key disaccharide intermediate could not be resolved by alterations in the reaction conditions; incorporation of the required amide earlier in the synthesis failed to lead to disaccharide products. Employing a phthalimide as nitrogen protecting group has successfully produced a glycosyl donor precursor that will only require ring opening rather than the troublesome reduction/acylation. Using a propargyl group to protect the anomeric position in the glysosyl acceptor has allowed for the attachment of the linker via a click reaction and subsequent deprotection reactions and FITC installation has produced one of the compounds required for comparison studies.

[发布机构] University:University of Birmingham;Department:School of Chemistry

[关键词] Q Science;QD Chemistry