Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Akinobu Senoo Last modified date:2023.01.31

Assistant Professor / Department of Pharmaceutical Health Care and Sciences / Faculty of Pharmaceutical Sciences


Papers
1. Jumpei Morimoto, Yasuhiro Fukuda, Daisuke Kuroda, Takumu Watanabe, Fumihiko Yoshida, Mizue Asada, Toshikazu Nakamura, Akinobu Senoo, Satoru Nagatoishi, Kouhei Tsumoto, Shinsuke Sando, A Peptoid with Extended Shape in Water., Journal of the American Chemical Society, 10.1021/jacs.9b04371, 141, 37, 14612-14623, 2019.09, The term "peptoids" was introduced decades ago to describe peptide analogues that exhibit better physicochemical and pharmacokinetic properties than peptides. Oligo(N-substituted glycine) (oligo-NSG) was previously proposed as a peptoid due to its high proteolytic resistance and membrane permeability. However, oligo-NSG is conformationally flexible, and ensuring a defined shape in water is difficult. This conformational flexibility severely limits the biological application of oligo-NSG. Here, we propose oligo(N-substituted alanine) (oligo-NSA) as a peptoid that forms a defined shape in water. The synthetic method established in this study enabled the first isolation and conformational study of optically pure oligo-NSA. Computational simulations, crystallographic studies, and spectroscopic analysis demonstrated the well-defined extended shape of oligo-NSA realized by backbone steric effects. This new class of peptoid achieves the constrained conformation without any assistance of N-substituents and serves as a scaffold for displaying functional groups in well-defined three-dimensional space in water, which leads to effective biomolecular recognition..
2. Sho Ito, Akinobu Senoo, Satoru Nagatoishi, Masahito Ohue, Masaki Yamamoto, Kouhei Tsumoto, Naoki Wakui, Structural Basis for the Binding Mechanism of Human Serum Albumin Complexed with Cyclic Peptide Dalbavancin., Journal of medicinal chemistry, 10.1021/acs.jmedchem.0c01578, 63, 22, 14045-14053, 2020.11, Cyclic peptides, with unique structural features, have emerged as new candidates for drug discovery; their association with human serum albumin (HSA; long blood half-life) is crucial to improve drug delivery and avoid renal clearance. Here, we present the crystal structure of HSA complexed with dalbavancin, a clinically used cyclic peptide. Small-angle X-ray scattering and isothermal titration calorimetry experiments showed that the HSA-dalbavancin complex exists in a monomeric state; dalbavancin is only bound to the subdomain IA of HSA in solution. Structural analysis and MD simulation revealed that the swing of Phe70 and movement of the helix near dalbavancin were necessary for binding. The flip of Leu251 promoted the formation of the binding pocket with an induced-fit mechanism; moreover, the movement of the loop region including Glu60 increased the number of noncovalent interactions with HSA. These findings may support the development of new cyclic peptides for clinical use, particularly the elucidation of their binding mechanism to HSA..
3. Tomoki Ota, Akinobu Senoo, Masumi Shirakawa, Hiroshi Nonaka, Yutaro Saito, Sho Ito, Go Ueno, Satoru Nagatoishi, Kouhei Tsumoto, Shinsuke Sando, Structural basis for selective inhibition of human serine hydroxymethyltransferase by secondary bile acid conjugate., iScience, 10.1016/j.isci.2021.102036, 24, 2, 102036-102036, 2021.02, Bile acids are metabolites of cholesterol that facilitate lipid digestion and absorption in the small bowel. Bile acids work as agonists of receptors to regulate their own metabolism. Bile acids also regulate other biological systems such as sugar metabolism, intestinal multidrug resistance, and adaptive immunity. However, numerous physiological roles of bile acids remain undetermined. In this study, we solved the crystal structure of human serine hydroxymethyltransferase (hSHMT) in complex with an endogenous secondary bile acid glycine conjugate. The specific interaction between hSHMT and the ligand was demonstrated using mutational analyses, biophysical measurements, and structure-activity relationship studies, suggesting that secondary bile acid conjugates may act as modulators of SHMT activity..