Universal polyethylene glycol linkers for attaching receptor ligands to quantum dots

Biologically active small molecule derivatives that can be conjugated to quantum dots have the promise of revolutionizing fluorescent imaging in biology. In order to achieve this several technical hurdles have to be surmounted, one of which is non-specific adsorption of quantum dots to cell membranes. Pegylating quantum dots has been shown to eliminate non-specific binding. Consequently it is necessary to develop a universal synthetic methodology to attach small molecule ligands to polyethylene glycol. These pegylated small molecules may then be conjugated to the surfaces of quantum dots. Ideally this universal strategy should be adaptable and be applicable to PEG chains of varying lengths. This paper describes the development of one such methodology and the synthesis of a pegylated derivative of the known 5HT2 agonist 1-(2-aminopropyl)-2,5-dimethoxy benzene. This compound was tested and found to be an agonist for the 5HT2A and 5HT2C receptor having EC50 values of 250 and 50 nM, respectively.

(i) Phthalimide, PPh3, DIAD; (ii)HNO3; (iii) DCC, NHS, tert-butyl 1-(4-(6-aminohexyl)-2,5-dimethoxyphenyl)propan-2-ylcarbamate; (iv) (a) TFA, (b) hydrazine hydrate.Figure optionsDownload as PowerPoint slide