Hunt for a Genetically Engineered, Rationally Designed, Stealth Peptide to Prevent Non-Specific Protein Interactions

Abstract

The objective of this study is to identify the best zwitterionic peptide as a tail of a fusion protein to preserve protein stability and bioactivity without immunogenicity. Two major strategies currently available to achieve this protective affect are (a) chemical conjugation and (b) genetic engineering. This study pursues the later approach. A major obstacle to the genetic engineering approach as identified by previous studies is related to expression yields which is unique to fusion proteins. For this study, Enhanced Green Fluorescent Protein (EGFP) was used as a model protein. The four amino acid chains (all 10kDa in length) were examined. They were fused to EGFP as a vehicle to study expression, purification, structure, and activity. The best candidate has the best expression yield and protein activity. The results of this study will be used as the starting point of ongoing research efforts aimed at increasing circulation time and decreasing the foreign body response for protective and therapeutic proteins; replacing PEGylation with these highly hydrated and bio-degradable peptides.