Abstract
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 conformationally constrained peptide with helix-loop-helix structure, termed “molecular-targeting HLH peptides”. Here, we introduce the molecular-targeting peptides that show antibody-like functions, high affinity and high specificity for the targeted proteins. Based on our technology of phage-displayed libraries for antibodies, we constructed a phage-displayed library of “molecular-targeting HLH peptides”, which was screened against a variety of disease-related proteins. The screened HLH peptides showed a strong binding affinity(KD of 4 nM) to the targeted protein and a long half-life(>2 weeks) in mouse sera, proving an enzyme-resistant property. Furthermore, immunization of the peptide to mice showed no induction of the antibody titer(non-immunogenic). The molecular-targeting HLH peptide is expected to be a new class of modalities of med-size medicines.
