PEGylation of Goldbody: PEG-aided conformational engineering of peptides on gold nanoparticles

It is still a great challenge to engineer flexible non-functional molecules into special conformations to carry out novel functions. Previously, we successfully restored the native conformations and functions of the flexible complementary-determining regions (CDRs) of antibodies on the surface of gold nanoparticles (AuNPs), and created a class of AuNP-based artificial antibodies, denoted as Goldbodies. Yet, in these Goldbodies, there are dozens of CDRs on one Goldbody. Herein, we show that the number of CDRs per Goldbody could be reduced by more than one order of magnitude, by replacing the majority of the CDRs with polyethylene glycol (PEG) with a molecular weight around 600 Da, while the native conformations and functions of the CDRs could still be restored on AuNPs. Also, we find that the PEG with two terminal –SH groups is much better than the PEG with a single –SH group for aiding the restoration of the native conformation of the CDRs on AuNPs. To demonstrate the potential generic applicability of the PEGylation in aiding conformational engineering of peptides, two PEGylated Goldbodies have been created, which can specifically recognize lysozyme and epidermal growth factor receptor, respectively. The PEGylated Goldbodies further prove the mechanism of conformational engineering and the “Confined Lowest Energy Fragments” (CLEFs) hypothesis, and pave the way for future applications of Goldbodies.