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 show some limitations, we have developed an alternative-binding molecule with non-immunoglobulin domain. The molecule is a helix- loop- helix peptide, which is stable against natural enzymes in vivo and is too small to be non-immunogenic. In our previous work, we have succeeded to develop a directed evolutionary process for improving efficiency of catalytic antibodies.1 Here, we apply our technology to construct a phage-displayed library of the helix-loop- helix peptides2 and then screened the library for G-CSF receptor. Finally, the screened binding peptides were cyclized by introduction of a disulfide- bond linkage into the N- and C-termini. The cyclic peptide showed strong binding affinity (Kd: 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. The semi-rational strategy, which combines directed evolution with de novo design, provides a new way to generate structured functional peptides as alternatives to antibody medicines.