Beyond Antibodies: Directed evolution of molecular-Targeting peptides in phage-displayed libraries of conformationally constrained Peptides

Abstract

WToday, antibodies are indisputably the most successful reagents in molecular targeting therapy. However, use of antibodies has been limited due to the biophysical properties and the cost to manufacture.To enable new applications where antibodies show some limitations, we have developed an alternative-binding molecule with non-immunoglobulin domain. The molecule is a helix-loop-helix peptide, MicroAntibody", which is stable against natural enzymes in vivo and is too small to be non-immunogenic. We constructed a phage-displayed library of MicroAntibodies. and screened the library for cytokine receptors. The obtained MicroAntibodies showed high affinity (Kd of nM range) and enzyme-resistant properties. The semi-rational strategy, which combines phage-displayed libraries with de novo designed peptides, provides a new way to generate structured functional peptides.