Synergistic Inhibition of Amyloid Formation by Conjugates of Gold Nanoparticles and Rationally Designed Single Domain Antibody
【摘要】：Amyloid formation plays a role in over 25 human disorders. Developing efficient inhibitors of amyloid formation has attached great interests in recent decades. However, many inhibitors are effective only in molar excess, or just retard the onset of amyloid fibrillation. Here we demonstrate that conjugating a rationally designed single domain antibody with gold nanoparticles yields highly potent inhibitors of amyloid formation. The single domain antibody is prepared by grafting small amyloidogenic peptide of human islet amyloid polypeptide (hIAPP) into the complementarity-determining regions (VH) of a single-domain antibody, and inhibit fibril assembly at low substoichiometric concentration. However, after it is conjugated with gold nanoparticles, which is typically believed to accelerate the fibril formation, the conjugates can completely inhibit the amyloid formation, at an even lower stoichiometric concentration of the antibody itself. The nanoparticles may accumulate the h IAPP, the further fibrillation of which is inhibited by the conjugated antibody, thus resulting in a synergistic inhibition of amyloid formation.