Abstract:
The invention provides methods for the production of single-chain Alphabody polypeptides having detectable binding affinity for, or detectable in vitro activity on, a viral protein of interest, which comprising the step of producing a single-chain Alphabody library comprising at least 100 different-sequence single-chain Alphabody polypeptides, wherein said Alphabody polypeptides differ from each other in at least one of a defined set of 5 to 20 variegated amino acid residue positions, and wherein said variegated amino acid residue positions are located at specific positions in one or more of the alpha-helices of the Alphabody or the linker fragment connecting two consecutive alpha-helices of the Alphabody polypeptides. The invention further provides Alphabodies obtainable by the methods of the invention and uses thereof.
Abstract:
Single-chain Alphabodies that comprise an alpha-helical binding region which mediates binding to a first fusion-driving region of a class-1 viral fusion protein and which structurally mimics a second fusion-driving region of said class-1 viral fusion protein, wherein said first and second fusion-driving regions of said class-1 viral fusion protein are regions which interact to drive the fusion between a virus displaying said class-1 viral fusion protein and a target cell.