A Study of Zwitterionic Polypeptide-Protein Conjugates

Abstract

Protein therapeutics has been an attractive approach to serve patients. However, the safety and efficacy of these products are limited by their immunogenicity, low circulation time, and instability. Conjugation is one of the most widely used methods to tackle these problems. PEG has been regarded as a gold standard in pharmaceutical industry for decades. However, problems like organ accumulation, susceptibility to oxidation, low surface packing density, pre-existing and triggered anti-PEG antibodies can cause serious advent effects. Herein, we modify proteins with zwitterionic peptides, aiming to study their in vitro binding affinity and in vivo pharmacokinetics and immunogenicity. Results show that this is a promising strategy to endow protein drugs with a stealth layer, allowing proteins to escape immune attack, increase half-life with no accelerated blood clearance effect, and exhibit super-low immunogenicity.