POLYVALENT GLYCAN-NAN OP ARTICLES AS MULTIFUNCTIONAL STRUCTURAL AND MECHANISTIC PROBES FOR VIRAL RECEPTORS, DC-SIGN AND DC-SIGNR

摘要

Multivalent protein-carbohydrate interactions are of critical importance in biology because they initiate the first contact between pathogens and host cells and ultimately lead to infection. Understanding the underlying structural and molecular mechanisms is key to develop specific, potent multivalent inhibitors that can block such interactions and prevent infection [1]. Two proteins that are of particular interest here are the tetrameric lectins, DC-SIGN [2] and DC-SIGNR [3]. They play a key role in facilitating the HIV and Ebola Virus infections by binding to the specific glycans found on the viral surface glycoproteins. Despite extensive research, their flexible, complex and multimeric structure has so far prevented X-ray crystal-lography from being applied to elucidate structural mechanisms. Herein we report the development of two types of glycan-nanoparticles, one is based on a fluorescent quantum dot (QD) and the other is based on a gold nanoparticle (AuNP), for probing multivalent DC-SIGN/R-glycan interactions via the fluorescence resonance energy transfer (FRET, Fig. 1A) and fluorescence quenching (Fig. 1B) readout.