Project 3. Peptide Therapeutics: Peptide-based Next-generation Drug design
In our body, biopolymers, such as proteins and nucleic acids form complex shapes and, thereby achieves biomolecular recognitions with each other to ehixit biomolecular functions. Understanding of the basis of the folding and bimolecular recognition is essential for producing new molecular tools for manipulating biological systems and realizing novel therapeutics. We are conducting the following research regarding such bimolecular folding and recognition.
Peptoids. Biomolecular recognition by synthetic oligomers
Synthetic oligomers called "peptoids" are known to be highly membrane-permeable peptidomimetics. The term "peptoids" indicates N-substituted peptides. Due to the lack of amide hydrogens, peptoids exhibit higher memrbane permeabilities than peptides. The regular peptoids are conformationally flexible due to the glycyl and β-alanyl backbones, which is potentially limiting the affinity of peptoids. Recently, by introducing chiral substituents on backbone carbons, we have succeeded in producing new peptoids that are conformationally constrained. We have demonstrated that the new peptoid, i.e. oligo(N-substituted alanines) can be utilized for ratinally designing molecules that recognize protein surfaces.