繰り返し配列を有するペプチドの構造活性相関研究
キーワード：ペプチド
2013.04.
| 野瀬 健（のせ たける） | データ更新日：2024.04.12 |
主な研究テーマ
環境ホルモンのリスク統括的評価法
キーワード：環境ホルモン 核内受容体 抗体 分子モデリング
1998.04.
キーワード：環境ホルモン 核内受容体 抗体 分子モデリング
1998.04.
７回膜貫通型受容体の活性化機構の解明
キーワード：GPCR 受容体
1994.04.
キーワード：GPCR 受容体
1994.04.
研究業績
主要原著論文
| 1. | Keitaro Suyama, Masayuki Murashima, Iori Maeda, Takeru Nose, Enhancement of Aggregate Formation Through Aromatic Compound Adsorption in Elastin-like Peptide (FPGVG)5 Analogs., Biomacromolecules, 10.1021/acs.biomac.3c00779, 24, 11, 5265-5276, 2023.11, Elastin-like peptides (ELPs) exhibit temperature-dependent reversible self-assembly. Repetitive sequences derived from elastin, such as Val-Pro-Gly-Val-Gly (VPGVG), are essential for the self-assembly of ELPs. Previously, we developed (FPGVG)5 (F5), in which the first valine residue in the VPGVG sequence was replaced with phenylalanine, which showed strong self-aggregation ability. This suggests that interactions through the aromatic amino acid residues of ELPs could play an important role in self-assembly. In this study, we investigated the thermoresponsive behavior of F5 analogs in the presence of aromatic compounds. Turbidimetry, spectroscopy, and fluorescence measurements demonstrated that aromatic compounds interacted with F5 analogs below the transition temperature and enhanced the self-assembly ability of ELPs by stabilizing amyloid-like structures. Furthermore, quantitative high-performance liquid chromatography analyses showed that the F5 analogs could adsorb and remove hydrophobic aromatic compounds from aqueous solutions during aggregate formation. These results suggested that the F5 analogs can be applicable as scavengers of aromatic compounds.. |
| 2. | Shogo Sumiyoshi, Keitaro Suyama, Naoki Tanaka, Takumi Andoh, Akihiko Nagata, Keisuke Tomohara, Suguru Taniguchi, Iori Maeda, Takeru Nose, Development of truncated elastin-like peptide analogues with improved temperature-response and self-assembling properties, Scientific Reports, 10.1038/s41598-022-23940-0, 12, 1, 2022.11, Abstract Functional peptides, which are composed of proteinogenic natural amino acids, are expected to be used as biomaterials with minimal environmental impact. Synthesizing a functional peptide with a shorter amino acid sequence while retaining its function is a easy and economical strategy. Furthermore, shortening functional peptides helps to elucidate the mechanism of their functional core region. Truncated elastin-like peptides (ELPs) are peptides consisting of repetitive sequences, derived from the elastic protein tropoelastin, that show the thermosensitive formation of coacervates. In this study, to obtain shortened ELP analogues, we synthesized several (Phe-Pro-Gly-Val-Gly)n (FPGVG)n analogues with one or two amino acid residues deleted from each repeat sequence, such as the peptide analogues consisting of FPGV and/or FPG sequences. Among the novel truncated ELP analogues, the 16-mer (FPGV)4 exhibited a stronger coacervation ability than the 25-mer (FPGVG)5. These results indicated that the coacervation ability of truncated ELPs was affected by the amino acid sequence and not by the peptide chain length. Based on this finding, we prepared Cd2+-binding sequence-conjugated ELP analogue, AADAAC-(FPGV)4, and found that it could capture Cd2+. These results indicated that the 16-mer (FPGV)4 only composed of proteinogenic amino acids could be a new biomaterial with low environmental impact.. |
| 3. | Shogo Sumiyoshi, Keitaro Suyama, Daiki Tatsubo, Naoki Tanaka, Keisuke Tomohara, Suguru Taniguchi, Iori Maeda, Takeru Nose, Metal ion scavenging activity of elastin-like peptide analogues containing a cadmium ion binding sequence, SCIENTIFIC REPORTS, 10.1038/s41598-022-05695-w, 12, 1, 2022.02, [URL], The development of simple and safe methods for recovering environmental pollutants, such as heavy metals, is needed for sustainable environmental management. Short elastin‐like peptide (ELP) analogues conjugated with metal chelating agents are considered to be useful as metal sequestering agents as they are readily produced, environment friendly, and the metal binding domain can be selected based on any target metal of interest. Due to the temperature dependent self‐assembly of ELP, the peptide‐based sequestering agents can be transformed from the solution state into the particles that chelate metal ions, which can then be collected as precipitates. In this study, we developed a peptide‐based sequestering agent, AADAAC‐(FPGVG)4, by introducing the metal‐binding sequence AADAAC on the N‐terminus of a short ELP, (FPGVG)4. In turbidity measurements, AADAAC‐ (FPGVG)4 revealed strong self‐assembling ability in the presence of metal ions such as Cd2+ and Zn2+. The results from colorimetric analysis indicated that AADAAC‐(FPGVG)4 could capture Cd2+ and Zn2+. Furthermore, AADAAC‐(FPGVG)4 that bound to metal ions could be readily recycled by treatment with acidic solution without compromising its metal binding affinity. The present study indicates that the fusion of the metal‐binding sequence and ELP is a useful and powerful strategy to develop cost‐ effective heavy metal scavenging agents with low environmental impacts.. |
| 4. | Suyama Keitaro, Mawatari Mika, Tatsubo, Daiki, Maeda Iori, Nose Takeru, 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, Elastin comprises hydrophobic repetitive sequences, such as Val-Pro-Gly-Val-Gly, which are thought to be important for the temperature-dependent reversible self-association (coacervation). Elastin and elastin-like peptides (ELPs), owing to their characteristics, are expected to be applied as base materials for the development of new molecular tools, such as drug-delivery system carrier and metal-scavenging agents. Recently, several studies have been reported on the dendritic or branching ELP analogues. Although the topological difference of the branched ELPs compared to their linear counterparts may lead to useful properties in biomaterials, the available information regarding the effect of branching on molecular architecture and thermoresponsive behavior of ELPs is scarce. To obtain further insight into the thermoresponsive behavior of branched ELPs, novel ELPs, such as nitrilotriacetic acid (NTA)-(FPGVG) n conjugates, that is, (NTA)-Fn analogues possessing 1-3 (FPGVG) n (n = 3, 5) molecule(s), were synthesized and investigated for their coacervation ability. Turbidity measurement of the synthesized peptide analogues revealed that (NTA)-Fn analogues showed strong coacervation ability with various strengths. The transition temperature of NTA-Fn analogues exponentially decreased with increasing number of residues. In the circular dichroism measurements, trimerization did not alter the secondary structure of each peptide chain of the NTA-Fn analogue. In addition, it was also revealed that the NTA-Fn analogue possesses one peptide chain that could be utilized as metal-scavenging agents. The study findings indicated that multimerization of short ELPs via NTA is a useful and powerful strategy to obtain thermoresponsive molecules.. |
| 5. | 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, [URL], 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.. |
| 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, [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.. |
| 7. | Daiki Tatsubo, Keitaro Suyama, Masaya Miyazaki, Iori Maeda, Takeru Nose, Stepwise Mechanism of Temperature-Dependent Coacervation of the Elastin-like Peptide Analogue Dimer, (C(WPGVG)3)2, Biochemistry, 10.1021/acs.biochem.7b01144, 57, 10, 1582-1590, 2018.02, [URL]. |
| 8. | 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, 22, 236-243, 2016.03. |
| 9. | Iori Maeda, Suguru Taniguchi, Noriko Watanabe, Asako Inoue, Yuko Yamazaki, Takeru Nose, Design of Phenylalanine-Containing Elastin-Derived Peptides Exhibiting Highly Potent Self-Assembling Capability , Protein & Peptide Letters, 10.2174/092986652210150821170703, 22, 10, 939-939, 2015.08, In this study, we developed a series of Phe-containing elastin-derived peptide-analogs, (Phe-Pro-Gly-Val-Gly)n (n = 1–5) and analyzed their reversible coacervation properties. Compared to the native elastin-derived repeating peptide sequence ((Val-Pro-Gly-Val-Gly)10), one of the Phecontaining 5-mer repeating peptide sequences ((Phe-Pro-Gly-Val-Gly)5) clearly exhibited stronger coacervation properties. The coacervation of (Phe-Pro-Gly-Val-Gly)5 is nearly the same as that of polypeptides (Val-Pro-Gly-Val-Gly)n (n > 40). Although large molecular weights (>10,000 Da) are generally required for the coacervation of elastin-derived peptides, (Phe-Pro-Gly-Val-Gly)5 exhibited reversible coacervation properties despite its low molecular weight (MW = 2,305 Da). High performance liquid chromatography (HPLC) and circular dichroism (CD) analysis revealed that (Phe-Pro-Gly-Val-Gly)5 has high hydrophobicity and an ordered structure with a type II β-turn, which contributes to the strong coacervation ability of the peptide. In addition, (Phe-Pro-Gly-Val-Gly)5 exhibited an effective particle size distribution (60–70 nm) at body temperature (37°C) and a dispersed small particle size similar to that of the monomer peptides at low temperatures. These properties, along with its small size and simple design, render the peptide suitable for use in biomaterials, including drug-delivery carriers.. |
| 10. | Iori Maeda, Suguru Taniguchi, Junko Ebina, Noriko Watanabe, Takao Hattori, Takeru Nose, Comparison between Coacervation Property and Secondary Structure of Synthetic Peptides, Ile-containing Elastin-derived Pentapeptide Repeats, Protein and Peptide Letters, 10.2174/0929866511320080007, 20, 8, 905-910, 2013.08, A series of Ile-containing elastin-derived peptide-analogs, (Ile-Pro-Gly-Val-Gly)n (n=7–10) possessing remarkable and reversible coacervation property were newly synthesized. In comparison with the known elastin-derived peptideanalogs, which were so-called polypeptides, the obtained 35 to 50 mer peptides, (IPGVG)n (n=7–10) were significantly low molecular sized-polypeptides. However, they clearly exhibited coacervation property as same as the polypeptides did. Because of their low molecular size, spectrographic analyses of (IPGVG)n (n=7–10) became feasible to carry out. As results of secondary structural analyses by CD and FT-IR, it was found that the coacervation property of the peptides is clearly attributed to the ordered secondary-structures, mainly, type II β–turn.. |
| 11. | Mitsuhiro Nishigori, Takeru Nose, Yasuyuki Shimohigashi, Highly Potent Binding and Inverse Agonist Activity of Bisphenol A Derivatives for Retinoid-related Orphan Nuclear Receptor RORg, Toxicol. Lett.,, 212, 2, 205-211, 2012.05. |
| 12. | Nose T., Tokunaga T., and Shimohigashi Y., Exploration of endocrine-disrupting chemicals on estrogen receptor α by the agonist/antagonist differential-docking screening (AADS) method: 4-(1-Adamantyl)phenol as a potent endocrine disruptor candidate, Toxicol. Lett.,, in press, 2009.11. |
主要総説, 論評, 解説, 書評, 報告書等
| 1. | 野瀬 健, 下東康幸 , ペプチド性GPCRリガンドの高効率構造活性相関解析研究, 遺伝子医学 MOOK, (12), 274-282 (2012)., 2012.03. |
主要学会発表等
学会活動
学協会役員等への就任
2017.11～2019.11, 日本生化学会, 代議員.
2018.06～2023.05, 環境ホルモン学会, 評議員.
2016.05～2023.05, 日本生化学会九州支部, 評議員.
2009.03～2010.02, 日本化学会九州支部, 幹事.
2005.10～2006.09, 日本生化学会九州支部, 幹事.
学会大会・会議・シンポジウム等における役割
2018.12.03～2019.12.07, 10th International Peptide Symposium, nternational Program Committee and Local Organizing Committee.
2016.05.16～2016.05.17, 平成28年度日本生化学会九州支部例会, 座長（Chairmanship）.
2012.11.07～2012.11.09, 第49回ペプチド討論会, 座長（Chairmanship）.
2012.05.26～2012.05.27, 平成24年度日本生化学会九州支部例会, 座長（Chairmanship）.
2011.09.27～2011.09.29, 第48回ペプチド討論会, 座長（Chairmanship）.
2009.11.04～2009.11.06, 第46回ペプチド討論会, 座長（Chairmanship）.
2009.05.16～2009.05.17, 平成21年度日本生化学会九州支部例会, 座長（Chairmanship）.
2008.10.29～2008.10.31, 第45回ペプチド討論会, 座長（Chairmanship）.
2008.05.01～2008.05.02, 平成20年度日本生化学会九州支部例会, 座長（Chairmanship）.
2007.05.01～2007.05.02, 平成19年度日本生化学会九州支部例会, 座長（Chairmanship）.
2004.05.26～2004.05.27, 平成15年度日本生化学会九州支部例会, 座長（Chairmanship）.
2013.09.02～2013.09.03, 第13回泉屋コロキウム, 世話人.
2009.11.04～2009.11.06, 第46回日本ペプチド討論会, 実行委員.
2009.07.11～2009.07.11, 第４６回化学関連支部合同大会, 実行委員.
2009.07.11～2009.07.11, 第２０回産学ユースフォーラム, 実行委員.
2009.05.29～2009.05.30, 19th Joint Seminar between The Kyushu Branch of Chemical Society of Japan and the Busan Branch of the Korean Chemical Society, 世話人.
2009.01.23～2009.01.23, 第12回ペプチドフォーラム－ペプチドサイエンスの最前線－, 実行委員.
2007.08.06～2007.08.07, 第７回泉屋コロキウム, 世話役.
2006.05.16～2006.05.17, 平成18年度日本生化学会九州支部シンポジウム, 幹事.
2006.05.16～2006.05.17, 平成18年度日本生化学会九州支部例会, 幹事.
2004.11～2005.04, First Asia-Pacific International Peptide Symposium, Secretary-General.
学術論文等の審査
| 年度 | 外国語雑誌査読論文数 | 日本語雑誌査読論文数 | 国際会議録査読論文数 | 国内会議録査読論文数 | 合計 |
|---|---|---|---|---|---|
| 2022年度 | 3 | 3 | |||
| 2021年度 | 3 | 0 | 0 | 2 | 5 |
| 2020年度 | 2 | 1 | 0 | 2 | 5 |
| 2019年度 | 2 | 0 | 0 | 0 | 2 |
| 2018年度 | 5 | 0 | 0 | 0 | 5 |
| 2017年度 | 2 | 2 | |||
| 2016年度 | 1 | 1 | |||
| 2015年度 | 1 | 1 | |||
| 2014年度 | 1 | 1 | |||
| 2013年度 | 2 | 2 | 4 | ||
| 2011年度 | 5 | 2 | 7 | ||
| 2010年度 | 4 | 2 | 6 | ||
| 2009年度 | 6 | 2 | 8 | ||
| 2008年度 | 2 | 2 | 4 | ||
| 2007年度 | 2 | 2 | 4 | ||
| 2006年度 | 1 | 3 | 4 |
その他の研究活動
受賞
第15回井上研究奨励賞, 公益法人井上科学振興財団, 1998.12.
日本ペプチド学会奨励賞, 日本ペプチド学会, 2002.10.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2020年度～2023年度, 挑戦的研究（開拓）, 代表, 天然タンパク質資源の有効活用を目指した機能性マイクロ粒子捕集素材の開発.
2019年度～2021年度, 基盤研究(B), 代表, 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.
2019年度～2019年度, 基盤研究(B), 分担, 新世代ビスフェノールのシグナル毒性を増強する核内受容体協働作用機構の解明.
2017年度～2018年度, 挑戦的研究（萌芽）, 代表, 天然アミノ酸を用いた低環境負荷型イオン回収ペプチドの開発.
2015年度～2018年度, 基盤研究(B), 代表, 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, 代表, 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.
2010年度～2014年度, 基盤研究(S), 分担, 新世代ビスフェノールの核内受容体を介したシグナル毒性.
2007年度～2009年度, 基盤研究(A), 分担, 核内受容体ERRγを介したビスフェノールAの低用量効果の解明.
2005年度～2007年度, 若手研究(A), 代表, クロロベンゼン環およびブロモベンゼン環が誘起する強力な受容体結合力の解明.
2004年度～2006年度, 基盤研究(B), 分担, コンホメーション変化センシング抗体法による環境化学物質の核内受容体のリスク評価.
科学研究費補助金の採択状況(文部科学省、日本学術振興会以外)
2008年度～2010年度, 厚生労働科学研究費補助金 (厚生労働省), 分担, 受容体アッセイ４種からなるヒト核内受容体４８種すべてに対する化学物質リスク評価スキームの構築.
2005年度～2007年度, 厚生労働科学研究費補助金 (厚生労働省), 分担, 核内受容体結合能およびホルモン活性同時測定法による化学物質リスク評価.
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