Rational Design of Semi-Synthetic Protein Complexes with the Defined Oligomeric State

Abstract

Protein oligomers are ubiquitous in nature and play an essential role in various biological processes. Recently, there is an enormous interest to custom‐make synthetic protein oligomers through the bottom‐up approach. In this regard, genetic methods have made tremendous progress in the last decade. In comparison, only few chemical methods currently exist for this purpose. Herein, we report a modular synthetic strategy for the design of facially amphiphilic globular protein‐synthetic peptide conjugates. The self‐assembly of these bioconjugates is driven by strong hydrophobic interaction of the peptide domain. The size, molecular mass and oligomeric state of semi‐synthetic protein complexes strongly depend on size and surface charge of a globular protein as well as the length of the hydrophobic peptide domain. A systematic structure‐property relationship study of these semi‐synthetic proteins should shed more light on the understanding of various non‐covalent forces, which governs the oligomerization processes of naturally occurring proteins.