Monobody/Adnectin/FN3 Scaffold Library Construction
FN3 constitutes a small, monomeric natural β-sandwich protein with resemblance to a trimmed Ig VH domain. It consists of 94 amino acids and possesses seven β-strands, with three loops connecting the strands in a pairwise fashion at one end of the β-sheet (Figure). Notably, FN3 is one of the rare members of the Ig superfamily devoid of disulphide bonds. In contrast to antibodies, the fold does not rely on disulfide bonds, yet still displays high thermodynamic stability. Since disulfide bonds do not form in reducing intracellular environments, FN3 can be a good choice in such circumstances, yet its application is not limited to reducing environments.