Microantibody: Directed evolution ofMolecular-targeting Peptides in Phage-displayed Libraries

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Use of antibody medicines has been limited due to the biophysical properties, immunogenicity, non-cell permeability, high cost to manufacture, and so on. To enable new applications where antibodies showsome limitations, we have developed an alternative-binding molecule with non-immunoglobulin domain. The molecule is a helix- loop- helix peptide. In previous work, we constructed a phage-displayed library of the helix-loop-helix peptides and then screened the library for G-CSF receptor to obtain a molecular-targeting peptide. Here, we examined the ability of the binding peptide as an alternative to antibody medicines. The peptide showed strong binding affinity (K_d: 4 nM) to the receptor, an enzyme-resistant property(half-life: 15 days in mouse sera), and non-immunogenicity. This peptide is named “microAntibodes” due to having the same properties as those of antibodies. Furthermore, we examined to screen the library of helix-loop-helix peptides against VEGF to successfully gain a tight-binding peptide. The semi-rational strategy, which combines directed evolution with de novodesign, provides a new way to generate a post-antibody therapy.