キーワード：エラスチン ペプチド コアセルベーション
|巣山 慶太郎（すやま けいたろう）||データ更新日：2019.06.11|
キーワード：核内受容体 受容体結合試験 蛍光トレーサー ビスフェノール
キーワード：核内受容体 受容体結合試験 蛍光トレーサー ビスフェノール
|1.||Xiaohui Liu, Hiroki Sakai, Mitsuhiro Nishigori, Keitaro Suyama, Tasuku Nawaji, Shin Ikeda, Makoto Nishigouchi, Hiroyuki Okada, Ayami Matsushima, Takeru Nose, Miki Shimohigashi, Yasuyuki Shimohigashi , Receptor-binding Affinities of Bisphenol A and Its Next-generation Analogs for Human Nuclear Receptors, Toxicology and Applied Pharmacology, https://doi.org/10.1016/j.taap.2019.114610, in press, 2019.06, An endocrine-disrupting chemical Bisphenol A (BPA) binds specifically to a nuclear receptor (NR) named ERRγ. Although the importance of receptor-binding evaluation for human NRs is often stressed, the binding characteristics of so-called next-generation (NextGen) bisphenol compounds are still poorly understood. The ultimate objective of this investigation was to evaluate BPA and its NextGen analogs for their abilities to bind to 21 human NRs, the greatest members of NRs for which tritium-labeled specific ligands were available. After establishing the detailed assay conditions for each NR, the receptor binding affinities of total 11 bisphenols were evaluated in competitive binding assays. The results clearly revealed that BPA and the NextGen bisphenols of BPAF, BPAP, BPB, BPC, BPE, and BPZ were highly potent against one or more of NRs such as CAR, ERα, ERβ, ERRγ, and GR, with IC50 values of 3.3–73 nM. These bisphenols were suggested strongly to be disruptive to these NRs. BPM and BPP also appeared to be disruptive, but less potently. BPF exhibited only weak effects and only against estrogen-related NRs. Surprisingly, most doubtful bisphenol BPS was supposed not to be disruptive. The NRs to which BPA and NextGen bisphenols did not bind were RARα, RARβ, RARγ, and VDR. PPARγ, RORα, RORβ, RORγ, RXRα, RXRβ, and RXRγ, exhibited very weak interaction with these bisphenols. The ten remaining NRs, namely, ERRγ, ERβ, ERα, CAR, GR, PXR, PR, AR, LXRβ, and LXRα, showed distinctly strong binding to some bisphenols in this order, being likely to have consequential endocrine-disruption effects..|
|2.||Keitaro Suyama, Daiki Tatsubo, Wataru Iwasaki, Masaya Miyazaki, Yuhei Kiyota, Ichiro Takahashi, Iori Maeda, Takeru Nose, Enhancement of self-aggregation properties of linear elastin-derived short peptides by simple cyclization
strong self-aggregation properties of cyclo[FPGVG]n, consisting only of natural amino acids, Biomacromolecules, 10.1021/acs.biomac.8b00353, 19, 8, 3201-3211, 2018.06, [URL], Elastin-like peptides (ELP) consist of distinctive repetitive sequences, such as (VPGVG)n, exhibit temperature-dependent reversible self-assembly (coacervation), and have been considered to be useful for the development of thermo-responsive materials. Further fundamental studies evaluating coacervative properties of novel nonlinear ELPs could present design concepts for new thermo-responsive materials. In this study, we prepared novel ELPs, cyclic (FPGVG)n (cyclo[FPGVG]n, n = 1-5), and analyzed its self-assembly properties and structural characteristics. Cyclo[FPGVG]n (n = 3-5) demonstrated stronger coacervation capacity than the corresponding linear peptides. The coacervate of cyclo[FPGVG]5 was able to retain water-soluble dye molecules at 40°C, which implied that cyclo[FPGVG]5 could be employed as a base material of DDS (Drug Delivery System) matrices and other biomaterials. The results of molecular dynamics simulations and circular dichroism measurements suggested that a certain chain length was required for cyclo[FPGVG]n to demonstrate alterations in molecular structure that were critical to the exhibition of coacervation..
|3.||Keitaro Suyama, Daiki Tatsubo, Hitoshi Kesamaru, Iori Maeda, Takeru Nose, Coacervation Property and Structural Analysis of Cyclic Analogs of Elastin-derived Peptide (FPGVG)n, Peptide Science 2016, 101-102, 2017.03, The elastin-derived peptide analog, (FPGVG)5, demonstrates a temperature- dependent self-association (coacervation) property. In this study, we prepared cyclic (FPGVG)n (n=1-5) analogs and investigated their coacervation and structural properties to assess their potential for use as a biomaterial. We found that the cyclic (FPGVG)n (n=3-5) analogs exhibited high coacervation ability. The results from the molecular dynamics simulation suggest that turn structures were important for coacervation of elastin-derived cyclic peptide analogs..|
|4.||Keitaro Suyama, Hitoshi Kesamaru, Daiki Tatsubo, Takeru Nose, Coacervation Properties and Structural Analysis of Aminobenzoyl-labeled Fluorescent Elastin-derived Peptides, Peptide Science 2015, 293-294, 2016.03, The elastin-derived peptide analog, (FPGVG)5, demonstrates a temperature- dependent self-association (coacervation) property. In this study, we prepared fluorescent-labeled (FPGVG)5 analogs, and evaluated their coacervation and fluorescent properties in order to assess their potential for use as a base material for fluorescent thermometers. We found that the fluorescent-labeled (FPGVG)5 analogs exhibited high coacervation ability. Results from the molecular dynamics calculation suggest that the fluorescent group is exposed on the surface of the molecule..|
|5.||Daiki Tatsubo, Keitaro Suyama, Takeru Nose, Fluorescence Analysis Using a Molecular Probe 1,8-ANS for Elucidation of the Molecular Mechanisms Underlying Coacervation of a Tryptophan-containing Elastin derived Dimeric Peptide, Peptide Science 2015, 95-96, 2016.03, A tryptophan-containing elastin-derived dimeric peptide (C(WPGVG)3)2 shows potent self-assembly activity. To elucidate the underlying coacervation mechanisms, we measured the fluorescence of (C(WPGVG)3)2 by using 1,8-ANS as a fluorescent probe. The results revealed that the peptide forms microaggregates at temperature and concentration lower than those at which visible coacervation occurs. These findings suggest that microaggregate formation is unrelated to the maturation of the coacervate drop, which is temperature-dependent..|
|6.||Keitaro Suyama, Suguru Taniguchi, Daiki Tatsubo, Iori Maeda, Takeru Nose, Dimerization effects on coacervation property of an elastin-derived synthetic peptide (FPGVG)5, Journal of Peptide Science, 10.1002/psc.2876, in press, 2016.03, A series of elastin-derived peptide (Phe-Pro-Gly-Val-Gly)5 dimers possessing high coacervation potential were synthesized. The new dimeric peptides showed significantly high coacervation ability compared to known elastin-derived peptide analogs. The molecular dynamics calculation results reveal that the dimeric peptides contain characteristic sheet-turnsheet motif involving a type II β-turn-like structure and form globular conformation..|
|7.||巣山 慶太郎, 田坪大来, 谷口 卓, 袈裟丸仁志, 前田衣織, 野瀬 健, Coacervation property and structural analysis of synthetic dimer peptides of aromatic amino acid containing elastin-derived peptides., Peptide Science 2014, 323-324, 2015.03, It has been shown that elastin-derived peptides containing aromatic amino acids, (FPGVG)n and (WPGVG)n, demonstrate coacervation at small repetition numbers (n = 3–5). In this study, we prepared dimer peptides of (FPGVG)5 and (WPGVG)3 and evaluated their coacervation properties. The coacervation ability of the peptides was significantly enhanced by the dimerization. The results of molecular dynamics calculation suggest that the sheet-turn-sheet motif is important for the self-assembly of FPGVG-related peptides..|
|8.||巣山 慶太郎, 谷口 卓, 前田衣織, 田坪大来, 野瀬 健, Coacervation Property and Secondary Structure of Synthetic Dimer Peptides of Elastin-derived Pentapeptide Repeats
, Peptide Science 2013, 277-278, 2014.03, Elastin is the core protein of elastic fibers in the elastic tissues, such as arterial walls, lungs, and skin, and plays an essential role in tissue biomechanics, providing the extensibility and condensability. Elastin shows self-association, which is referred as coacervation, under physiological conditions. Coacervation property of elastin characterized by reversible association/dissociation phenomena is considered to be important for its elasticity. Tropoelastin, the precursor protein of elastin, contains characteristic repetitive sequences in its hydrophobic regions. The pentapeptide sequence, Val-Pro-Gly-Val-Gly (VPGVG), is one of the repeating sequences, and presents in almost all mammal species analyzed so far. To clarify the mechanism of elastin’s elasticity, many studies about coacervation properties of elastin-derived peptide-analogs have been conducted. Many previous studies reported that large molecular size was needed for coacervation of elastin-derived peptides. For instance, (VPGVG)n demonstrated the coacervation property only when they had large numbers of repetition (n>40). Recently, we developed the synthetic hydrophobic oligomers (IPGVG)n and (FPGVG)n, and reported that they demonstrate coacervation at significantly smaller repetition numbers (n=5~7). Because of their low molecular size, these analogs are expected to be useful as model peptides for structure analysis and base materials for developing various biomedical products, skin substitutes, synthetic vascular grafts, and drug delivery systems.
In this study, to obtain more short coacervatable peptides, we synthesized dimers of pentapeptide (FPGVG)5 and investigated their coacervation property and secondary structures. To produce dimer peptides, cysteine-conjugated pentapeptide Cys-(FPGVG)5 and (FPGVG)5-Cys were synthesized by the solid-phase method using Fmoc strategy. By aerobic oxidation reaction of each Cys-peptide, homodimers, linked by disulfide bond, were obtained. Synthesized peptides were purified by HPLC and analyzed by MALDI-TOF- MS. The dimer peptides clearly showed coacervation around 15˚C in the condition at 10 mg/ml, whereas (FPGVG)5 required rather higher temperature and at least 20 mg/ml of peptide to demonstrate coacervation. These results indicated that the dimerization of elastin-derived peptide-analogs significantly enhanced the coacervation ability of (FPGVG)5. Furthermore, these dimer peptides showed reversible temperature-dependent conformation change in CD measurement..
|9.||Kanako Nishio, Hirokazu Nishimura, Keitaro Suyama, Takeru Nose, Yasuyuki Shimohigashi, Halogenated Phe-containing endomorphin-2 analogs with mixed agonist and antagonist activities, Peptide Science 2012, in press, 2013.03.|
|10.||Yumi Kramitsu, Hirokazu Nishimura, Ryo Nakamura, Keitaro Suyama, Kazuhiro Matsumoto, Takeru Nose, Yasuyuki Shimohigashi, High-precision binding assay procedure of tachykinin receptor NK-1 for highly potent substance P analogs, Peptide Science 2012, in press, 2013.03.|
|11.||Ryo Nakamura, Hirokazu Nishimura, Keitaro Suyama, Takeru Nose, Yasuyuki Shimohigashi, The Effect of Halogenation of Phe-Phenyl Group of Two Consecutive Phe Residues Present in Neuropeptide Substance P on Its Specific Receptor Interaction, Peptide Science 2011, 157-158, 2012.03.|
|12.||Kanako Nishio, Hirokazu Nishimura, Keitaro Suyama, Yoshinori Abe, Takeru Nose, Ayami Matsushima, Yasuyuki Shimohigashi, Effects of the Halogenation of Phe-Phenyl Group of Two Consecutive Residues in Endomorphin-2 on the Interaction with the μ-Opioid Receptors, Peptide Science 2011, 171-172, 2012.03.|
|13.||Keitaro Suyama, Kazuhiro Matsumoto, Tsutomu Katsuki, Asymmetric Lewis Acid Catalysis of Aluminum(salalen) Complexes: Friedel-Crafts Reaction of Indole, Heterocycles, 10.3987/COM-08-S(F)93, 77, 817-824, 2009.02.|
|14.||Keitaro Suyama, Yoshifumi Sakai, Kazuhiro Matsumoto, Tsutomu Katsuki, Highly Enantioselective Hydrophosphonylation of Aldehydes: Base-Enhanced Aluminum-salalen Catalysis, Angewante Chemie, International Edition, 10.1002/anie.200905158, 49, 797-799, 2010.01.|
主要総説, 論評, 解説, 書評, 報告書等
2018.09.12～2018.09.12, 第18回泉屋コロキウム, 世話人補佐・会計.
2015.05.16～2015.05.17, 平成27年度日本生化学会九州支部例会, 座長（Chairmanship）.
2015.08.08～2015.08.08, 平成27年度理学部前期特別談話会, 座長（Chairmanship）.
2016.02.18～2016.02.19, 平成27年度修士論文講演会, 座長（Chairmanship）.
2014.03.10～2014.03.10, リスクサイエンス研究フォーラム2014, 会場設営・備品搬入および搬出の監督.
2013.09.02～2013.09.03, 第13回泉屋コロキウム, 世話人補佐・会計.
優秀ポスター発表賞, 泉屋コロキウム, 2011.09.
2019年度～2021年度, 基盤研究(B), 分担, 自己凝集性ペプチドの可逆コアセルベーションによる環境汚染物質吸着システムの開発.
2015年度～2018年度, 基盤研究(B), 分担, ビスフェノールＡの化学修飾が引き起こす核内受容体結合力増強機構の解明.
2014年度～2015年度, 挑戦的萌芽研究, 分担, 自己凝集性ペプチドを基材とした金属イオン回収材の開発.