Elastin, a core protein of the elastic fibers, exhibits the coacervation (temperature-dependent reversible association/ dissociation) under physiological conditions. Because of this unique characteristic, elastin and elastin-derived peptides have been considered to be useful as base materials for developing various biomedical products, skin substitutes, synthetic vascular grafts and drug delivery systems.
In our recent studies, we newly developed a series of elastin-derived peptide dimers, (Cys-(Phe-Pro-Gly-Val-Gly)5)2 and (Cys-(Trp-Pro-Gly-Val-Gly)3)2, possessing a high coacervation potential. These novel dimeric peptides exhibited coacervation at significantly lower concentrations and temperatures than the commonly used elastin-derived peptide analogs; this result suggests that the coacervation ability of the peptides is enhanced by dimerization. On the basis of these findings, we are developing more potent elastin-derived peptide analogs with biological and chemical functions.
We conducted risk assessment studies on endocrine disrupting chemicals (EDCs) by using a combination of computational and biochemical techniques. Nuclear receptors (NRs) are the main target of EDCs and play a central role as transcription factors in biological processes. If chemicals that can bind to the ligand-binding domain (LBD) are identified, this information would be very helpful for identifying chemicals that can bind to NRs and cause serious disruptions in the endocrine system.
We established a novel screening method to study endocrine-disrupting chemicals by means of in silico docking calculations. We used the crystal structures of both agonist-bound LBDs and antagonist-bound LBDs as templates in the docking calculations, and estimated binding energies to discriminate between agonist and antagonist binding. This agonist/antagonist differential-docking screening (AADS) method is an approach that appears to predict both the binding ability and the agonist/antagonist function of chemicals for the target nuclear receptors.
The dipeptide inhibitor D-Leu-Phe-NHBzl (pF) inhibits chymotrypsin via a π-π stacking interaction between the Phe-phenyl group of the inhibitor and His57-imidazole ring at the active site of chymotrypsin. This p interaction is essential for inhibition. In this study, we considered whether the docking calculation based on the conventional molecular mechanics method was applicable to strengthening the inhibitory activity of the dipeptide inhibitor. On the basis of the calculations, we are going to design and synthesize tripeptide inhibitors and to perform in vitro enzyme-inhibition tests.
744 Motooka Nishi-ku Fukuoka 819-0395 Japan