Platform technologies

Helix-Loop-Helix Peptide (HLHP)

Invented by Professor Ikuo Fujii at Osaka Prefecture University (Distinguished Professor and Dean, School of Science), helix-loop-helix peptides are equipped with several excellent features as a drug modality.

3.5kDa New Modality

Our helix-loop-helix peptide shows an antibody-like high affinity to target proteins and PPI inhibitory activity

Helix-loop-helix peptides (MW ~3.5 kDa) possess a unique conformationally constrained structure. Its structural rigidity is ensured by hydrophobic interactions on the inside of two α-helices, a connecting loop, and the disulfide or chemically modified bridge on the other end of the helices. These peptides can bind to the targets with high affinity and effectively disrupt protein-protein interactions.

Resistant to Proteolysis, Non-Antigenic, Bi-Specific

Its size and unique conformation gives helix-loop-helix peptides strong advantages as a drug modality

Largely owing to its rigid conformation, helix-loop-helix peptides are resistant to proteolysis even in the bloodstream. It has also been confirmed that helix-loop-helix peptides are not antigenic as predicted by its size. Helix-loop-helix peptides can bind to target proteins with two binding regions (loop and α-helix of C-terminal side) and this bi-specific nature may allow us to produce bi-functional drugs.

> 1010 library size

With random mutagenesis, helix-loop-helix peptides can easily achieve the library size of >1010

The library of this size easily exceeds that of small molecules by 2-3 orders of magnitude, and is conveniently screened against a target protein by phage-display. We have constructed an extremely diverse library of helix-loop-helix peptides; random mutations can be introduced into the α-helix of C-terminal side as well as in the connecting loop. We can also construct a new library based on the property of proposed targets. Alternatively, the peptides can be rationally designed.

100% success rate

With increased library size, we have achieved ~100% success rate

Through experiences with pharmaceutical partners, we have succeeded in increasing the number of variable residues in helix-loop-helix peptide. The extremely diverse libraries for helix-loop-helix peptide have enabled us to achieve near 100% success rate in identifying high affinity binders so far. With helix-loop-helix peptides, you can target any protein without information about the structure of the target protein.

n ~ pM Activity

Advanced technology allows us to produce helix-loop-helix peptides with sub-nanomolar range affinity

With increasing randomization capabilities, we can generate variations of initial hits to increase the affinity. We have constantly achieved the affinity in the sub-micromolar range against target proteins, and in a few cases, we obtained optimized helix-loop-helix peptides with sub-nanomolar affinity.

Tumor Targeting

The tumor targeting helix-loop-helix peptide was precisely localized to tumors

Drug delivery system (DDS) is a focus of current drug discovery field and we are up to the offer for collaboration from this side with the helix-loop-helix-peptide technology. We have found that our tumor-targeting peptides are localized in tumors. Conjugated with highly active anti-cancer drugs, the peptide will turn into very efficient tumor killing reagent.

Presentation Materials: A New Peptide Drug Modality; Helix-Loop-Helix Technology