Engineered Two‐Helix Small Proteins for Molecular Recognition

Abstract
Less is more: By starting with a high‐affinity HER2‐binding 3‐helix affibody molecule, we successfully developed 2‐helix small protein binders with 5 nM affinities by using a combination of several different strategies. Our efforts clearly suggest that 2‐helix small proteins against important tumor targets can be obtained by rational protein design and engineering.