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Keitaro Suyama Last modified date:2021.06.17

Assistant Professor / Laboratory of Molecular Biochamistry
Division for Experimental Natural Science
Faculty of Arts and Science




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Homepage
https://kyushu-u.pure.elsevier.com/en/persons/keitaro-suyama
 Reseacher Profiling Tool Kyushu University Pure
Phone
092-802-5849
Academic Degree
Doctor of Science
Country of degree conferring institution (Overseas)
No
Field of Specialization
biochemistry, organic chemistry
Research
Research Interests
  • Coacervation Property and Secondary Structure of the Elastin-derived Synthetic Dimer Peptides
    keyword : elastin peptide coacervation
    2013.03~2017.03.
  • Asymmetric reaction caltalyzed by aluminum(salalen) complex
    keyword : asymmetric catalytic reaction, aluminum(salalen) complex
    2006.04~2009.03.
  • Probe exploitation for essential nuclear receptor-binding assay
    keyword : nuclear receptor, receptor binding assay, fluorescent probe, bisphenol
    2009.04.
Academic Activities
Reports
1. In order to provide new and field crossing subjects for active learners, we developed a new experimental subject focusing on amino acids. To strengthen the learners’ thinking power in a manner that is not limited to the confines of the existing subjects, this subject was designed to contain a variety of experiments concerning chemistry, biology, nutrition, and computer science. In the second semester of 2015, we carried out the subject as a trial class. Twelve students belonging to five different undergraduate schools attended this course. To achieve the purpose of this class, we provided eight lessons incorporating lectures, basic experiments, computer simulations, and observations using analytical equipment. To evaluate this subject, we surveyed students’ attitudes toward the class. In the questionnaire responses, we found that many students felt that the number of lectures containing experimental activities should be increased in general subjects to help them grow as active learners..
Papers
1. Keitaro Suyama, Mika Mawatari, Daiki Tatsubo, Iori Maeda, Takeru Nose., Simple Regulation of the Self-Assembling Ability by Multimerization of Elastin-Derived Peptide (FPGVG)n Using Nitrilotriacetic Acid as a Building Block., ACS Omega, 10.1021/acsomega.0c06140. , 6, 8, 5705-5716, 2021.02.
2. Xiaohui Liu, Keitaro Suyama, Takeru Nose, Miki Shimohigashi, Yasuyuki Shimohigashi, Bisphenol-C is the strongest bifunctional ERα-agonist and ERβ-antagonist due to magnified halogen bonding, PLoS ONE, https://doi.org/ 10.1371/journal.pone.0246583, 16, 2, e0246583, 2021.02.
3. Keitaro Suyama, Shuhei Kaneko, Hitoshi Kesamaru, Xiaohui Liu, Ayami Matsushima, Yoshimitsu Kakuta, Takashi Okubo, Kazumi Kasatani, Takeru Nose, Evaluation of the Influence of Halogenation on the Binding of Bisphenol A to the Estrogen-Related Receptor γ, Chemical Research in Toxicology, 10.1021/acs.chemrestox.9b00379, 33, 4, 889-902, 2020.04, Halogenation of organic compounds is one the most important transformations in chemical synthesis and is used for the production of various industrial products. A variety of halogenated bisphenol analogs have recently been developed and are used as alternatives to bisphenol A (BPA), which is a raw material of polycarbonate that has adverse effects in animals. However, limited information is available on the potential toxicity of the halogenated BPA analogs. In the present study, to assess the latent toxicity of halogenated BPA analogs, we evaluated the binding and transcriptional activities of halogenated BPA analogs to the estrogen-related receptor γ(ERRγ), a nuclear receptor that contributes to the growth of nerves and sexual glands. Fluorinated BPA analogs demonstrated strong ERRγbinding potency, and inverse antagonistic activity, similar to BPA. X-ray crystallography and fragment molecular orbital (FMO) calculation revealed that a fluorine-substituted BPA analog could interact with several amino acid residues of ERRγ-LBD, strengthening the binding affinity of the analogs. The ERRγbinding affinity and transcriptional activity of the halogenated BPAs decreased with the increase in the size and number of halogen atom(s). The IC50 values, determined by the competitive binding assay, correlated well with the binding energy obtained from the docking calculation, suggesting that the docking calculation could correctly estimate the ERRγbinding potency of the BPA analogs. These results confirmed that ERRγhas a ligand binding pocket that fits very well to BPA. Furthermore, this study showed that the binding affinity of the BPA analogs can be predicted by the docking calculation, indicating the importance of the calculation method in the risk assessment of halogenated compounds..
4. Xiaohui Liu, Keitaro Suyama, Junichi Shiki, Kohei Torikai, Takeru Nose, Miki Shimohigashi, Yasuyuki Shimohigashi, Bisphenol AF
Halogen bonding effect is a major driving force for the dual ERα-agonist and ERβ-antagonist activities, Bioorganic and Medicinal Chemistry, 10.1016/j.bmc.2019.115274, 28, 3, 2020.02, 17β-Estradiol (E2) is a natural steroid ligand for the structurally and physiologically independent estrogen receptors (ERs) ERα and ERβ. We recently observed that CF3-containing bisphenol AF (BPAF) works as an agonist for ERα but as an antagonist for ERβ. Similar results were also observed for the CCl3-containing bisphenol designated as HPTE. Both BPAF and HPTE are comprised of a tri-halogenated methyl group in the central alkyl moiety of their bisphenol structures, which strongly suggests that halogens contribute directly to the agonist/antagonist dual biological functions. We conducted this study to investigate the structure-activity relationships by assessing together newly synthesized CF3- and CBr3-containing bisphenol E analogs (BPE-X). We first tested bisphenols for their receptor binding ability and then for their transcriptional activities. Halogen-containing bisphenols were found to be fully active for ERα, but almost completely inactive for ERβ. When we examined these bisphenols for their inhibitory activities for E2 in ERβ, we observed that they worked as distinct antagonists. The ascending order of agonist/antagonist dual biological functions was BPE-F < BPE-Cl (HPTE) ≤ BPAF < BPE-Br, demonstrating that the electrostatic halogen bonding effect is a major driving force of the bifunctional ERα agonist and ERβ antagonist activities of BPAF..
5. 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..
6. 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, 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..
7. 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..
8. 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..
9. 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..
10. 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..
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
Presentations
1. 巣山 慶太郎, 清水真凜, 前田衣織, 野瀬 健, The effect of sequential modification of elastin-derived (FPGVG)n peptide analogs on self-assembly properties, 第100回日本化学会年会, 2020.03, Elastin-like peptides (ELPs), which consist of distinct repetitive sequences of elastin, exhibit temperature-dependent reversible self-assembly (coacervation) under physiological conditions. Due to this characteristic property, ELPs have been considered useful for the development of thermoresponsive biomaterials. Among ELPs, the pentapeptide sequence Val-Pro-Gly-Val-Gly (VPGVG) is the representative motif that exhibits coacervation. By mimicking this repetitive pentapeptide sequence, we have developed an elastin-derived short synthetic peptide, (FPGVG)n, that demonstrates stronger coacervation than (VPGVG)n. Although this peptide is potentially useful for developing stimuli-responsive biomaterials, the effects of sequential modification of ELPs on their coacervation activity are still unclear. In this study, (FPGVG)n-based peptide analogs whose phenylalanine residues were substituted with other amino acids were synthesized, and their coacervation properties were analyzed to elucidate the effect of the sequence on the self-association property.
The elastin-derived peptide (FPGVG)5 (F5) and F5-derived peptide analogs were successfully synthesized by the Fmoc solid phase method. Subsequently, the temperature-dependent coacervation properties of the synthetic peptides were evaluated by turbidity measurement. As a result, F5-analogs that contain aromatic amino acids (Tyr or Trp) as a substituent exhibited strong coacervation activity. When one of the Phe residues of F5 were substituted by a non-aromatic amino acid, the coacervation activity of the peptide significantly decreased, even if the replacement was a hydrophobic aliphatic amino acid. It was suggested that the coacervation activity of short ELPs is not simply determined by the hydrophobicity of the peptide and that interaction via aromatic amino acid residues was important for the coacervation activity of the peptides. It was also revealed that the coacervation activity of F5 was drastically affected by the substitution of a single amino acid residue.
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2. 巣山 慶太郎, 馬渡弥佳, 田坪大来, 前田衣織, 野瀬 健, Concentration Dependent Coacervation Property of Nonlinear Elastin-derived Peptide (FPGVG)n Analogs, 第56回ペプチド討論会, 2019.10, Elastin-like peptide (ELP) analogs demonstrate reversible temperature-dependent association (coacervation) under physiological conditions. Previously, we revealed that simply dimerized and cyclized short ELP analogs show stronger coacervation activity than monomeric and linear counterpart of them, respectively. In this study, we investigated concentration dependency of the transition temperature of nonlinear short ELPs to estimate their coacervation activity. It was revealed that the transition temperature of nonlinear ELPs could be described as the logarithmic function of peptide concentration. In addition, by using this quantitative relationship, it was able to compare and estimate the coacervation activity of artificial ELPs with different water solubility..
3. 巣山慶太郎・田坪大来・谷口 卓・前田衣織・野瀬 健, Development of Self-assembling Short Elastin-derived Peptide Analogs: Linear and Nonlinear (FPGVG)n Analogs, 10th International Peptide Symposium, 2018.12.
4. Self-assembly properties and structural analyses of fluorescent-labeled analogs of elastin-derived synthetic peptide (FPGVG)5.
5. Coacervation and fluorescence properties of fluorescent-labeled elastin-derived peptides.
6. 巣山 慶太郎, 田坪大来, 袈裟丸 仁志, 野瀬 健, Coacervation Properties and Structural Analysis of Aminobenzoyl-labeled Fluorescent Elastin-derived Peptides, 第52回ペプチド討論会, 2015.11, Biological reactions within living cells are affected by temperature. Therefore, mapping the intracellular temperature of living cells is expected to contribute to an improved understanding of cellular events and the establishment of novel therapeutics. Previously, Uchiyama et al. demonstrated intracellular temperature mapping based on a fluorescent polymeric thermometer consisting mainly of acrylamide derivatives. Elastin-derived peptides exhibit reversible self-association (coacervation) under physiological conditions. Therefore, it was considered that these peptides might serve as useful materials for the development of such a fluorescent thermometer. Recently, we reported that the short synthetic elastin-derived peptide (FPGVG)5 demonstrates coacervation, which suggests that fluorescent-labeled (FPGVG)5 peptides, in particular, may be useful as basic materials for developing a novel fluorescent peptide-based thermometer. In the present study, we synthesized fluorescent-labeled analogs of (FPGVG)5 and investigated their coacervation property and peptide conformation..
7. 巣山 慶太郎, 野瀬 健, 谷口 卓, 前田衣織, 河野敬一, エラスチン由来ペプチドダイマーの自己集合特性および立体構造の解析, 分子・物質合成PF H25年度シンポジウム , 2014.03.
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 the Elastin-derived Pentapeptide Repeat-related Peptide, 4th Asia-Pacific International Peptide symposium 2013/50th Japanese Peptide Symposium , 2013.11, Elastin is the core protein of elastic fibers in the elastic tissues plays an essential role in tissue biomechanics, providing the extensibility and condensability. Elastin shows coacervation (reversible association/dissociation phenomena) under physiological conditions. Tropoelastin, the precursor protein of elastin, contains characteristic repetitive sequences such as the pentapeptide sequence, Val-Pro-Gly-Val-Gly (VPGVG), in its hydrophobic regions. However, it was reported that large molecular size was needed for coacervation of elastin-derived peptide (VPGVG)n (numbers of repetition: n>40). Recently, we reported that synthetic hydrophobic oligomers (IPGVG)n and (FPGVG)n 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. In this study, to obtain more short coacervatable peptides, we synthesized dimers of pentapeptide (FPGVG)5 and investigated their coacervation property and secondary structures..
9. Keitaro Suyama, Kazuhiro Matsumoto, Tsutomu Katsuki, Asymmetric Lewis Acid Catalysis of Aluminum(salalen) Complexes: Friedel-Crafts Reaction of Indole, 19th Joint Seminar of the Busan Branch of the Korean Chemical Society and the Kyushu Branch of the Chemical Society of Japan, 2009.05.
Educational
Other Educational Activities
  • 2013.04.
  • 2013.06.