Chemoselective Immobilization of Peptides on Abiotic and Cell Surfaces at Controlled Densities

Abstract

We report herein a new and enabling approach for decorating both abiotic and cell surfaces with the extracellular matrix IKVAV peptide in a site-specific manner using strain promoted azide−alkyne cycloaddition. A cyclooctyne-derivatized IKVAV peptide was synthesized and immobilized on the surface of pancreatic islets through strain-promoted azide−alkyne cycloaddition with cell surface azides generated by the electrostatic adsorption of a cytocompatible poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) copolymer bearing azido groups (PP-N₃). Both “one-pot” and sequential addition of PP-N₃ and a cyclooctyne-derivatized IKVAV peptide conjugate enabled efficient modification of the pancreatic islet surface in less than 60 min. The ability to bind peptides at controlled surface densities was demonstrated in a quantitative manner using microarrays. Additionally, the technique is remarkably rapid and highly efficient, opening new avenues for the molecular engineering of cellular interfaces and protein and peptide microarrays.