Creation of glycoprotein imprinted self-assembled monolayers with dynamic boronate recognition sites and imprinted cavities for selective glycoprotein recognition

Glycoproteins are involved in the pathogenesis and development of many diseases and are used as biomarkers for disease diagnosis. It is highly desirable to develop highly sensitive and selective methods for the detection of glycoproteins without the use of antibodies. Imprinting of proteins represents one of the most challenging tasks. Glycoprotein imprinted self-assembled monolayers (SAMs) were created, for the first time, from an oligo(ethylene glycol) (OEG) terminated 1,2-dithiolane derivative linked through an alkyl chain incorporated with two amide groups (DHAP) and combined functional thiols of p-mercaptophenylboronic acid (PMBA) and p-aminothiophenol (PATP) in aqueous media, without use of polymerization initiators. Combined action of PMBA and PATP was essential for the development of boronate recognition sites for glycoproteins at the physiological pH, attributed to the water molecule-mediated Lewis acid–base interactions between the electron-deficient PMBA and the electron-rich PATP. DHAP played key roles not only in cementation of imprinted cavities by means of double hydrogen-bond networks through the amide groups but also in resistance to nonspecific protein binding by terminal OEG moieties, as well as hydrogen bond binding sites from the amide groups exposed to imprinted cavities. The created glycoprotein imprinted SAMs showed excellent recognition selectivity of target glycoproteins. The strategy for tailor-made glycoprotein imprinted SAMs explores a new avenue to the creation of intelligent biomaterials and fabrication of chemosensors.