研究者データベース
| 横井 康広(ヨコイ ヤスヒロ) |
| 先端生命科学研究院 |
| 助教 |
Last Updated :2024/05/09
基本情報
所属
職名
学位
科研費研究者番号
- 30898854
ORCID ID
Researcher ID
- J-5103-2017
J-Global ID
研究キーワード
研究分野
- ライフサイエンス / 生物有機化学
- ライフサイエンス / 構造生物化学
- ライフサイエンス / 薬系化学、創薬科学
- ナノテク・材料 / ケミカルバイオロジー
- ナノテク・材料 / 有機合成化学
- ナノテク・材料 / 生体化学
- ナノテク・材料 / ナノバイオサイエンス
職歴
学歴
所属学協会
研究活動情報
論文
- Ken Murakami, Daiki Kambe, Yasuhiro Yokoi, Hajime Wakui, Shun Hayakawa, Nozomi Hirane, Ryosuke Koide, Michiru Otaki, Noriko Nagahori, Shin-Ichiro NishimuraAdvanced NanoBiomed Research 3 12 2023年11月08日 [査読有り]
Human neuraminidase‐1 (NEU1) plays a much more profound function in human cancers than previously considered. It is demonstrated that cancer cell surface NEU1 is a desired gatekeeper for an innovative anticancer therapeutic nanomedicine enabling active drug‐targeting delivery by specific endocytosis into the cytoplasm. Nanosome, an antiadhesive nanoparticular shuttle, carrying multiple suicide substrates for NEU1 confers potent and universal inhibitory effects on the proliferation of human cancer cells, such as hepatocellular carcinoma (HCC) (HepG2, IC50 = 13.5 nM), lung cancer (A549, IC50 = 9.57 nM), and colon cancer (HT‐29, IC50 = 11.1 nM), in which irreversible inactivation of cell surface NEU1 is essential for the intracellular trafficking and subsequent lysosomal membrane permeabilization by nanosomal aggregation due to the formation of “sialidase corona” through irreversible inactivation of NEU1–NEU4 residing in lysosome. Nanomedicine targeting membrane‐tethered NEU1 allows efficient delivery of hydrophobic sorafenib (Nexavar), a RAF family kinase inhibitor for the treatment of advanced renal cell carcinoma and unresectable HCC at the recommended dose of 400 mg orally twice daily, into endolysosome, resulting in a potent and sustainable inhibition (IC50 = 3.1–6.2 nM at 24–96 h after coincubation) against HepG2 cell growth. - Hajime Wakui, Yasuhiro Yokoi, Chieko Horidome, Toyoyuki Ose, Min Yao, Yoshikazu Tanaka, Hiroshi Hinou, Shin-Ichiro NishimuraRSC Chemical Biology 4 8 564 - 572 2023年05月24日 [査読有り]
We unveil for the first time that pancreatic cancer cells (PANC-1) and secreted exosomes express MUC1 bearing cancer-relevant dynamic epitopes recognized specifically by an anti-MUC1 antibody (SN-131). - Kouta Shiratori, Yasuhiro Yokoi, Hajime Wakui, Nozomi Hirane, Michiru Otaki, Hiroshi Hinou, Tohru Yoneyama, Shingo Hatakeyama, Satoshi Kimura, Chikara Ohyama, Shin-Ichiro NishimuraRSC Advances 12 33 21385 - 21393 2022年08月03日 [査読有り]
Structure-defined synthetic glycopeptides allow the validation of glycopeptide biomarkers pre-determined from bottom-up glycoproteomics based on the selective reaction monitoring approach. - Ryosuke Koide, Nozomi Hirane, Daiki Kambe, Yasuhiro Yokoi, Michiru Otaki, Shin-Ichiro NishimuraBiomaterials 280 121314 - 121314 2021年12月09日 [査読有り]
- Yasuhiro Yokoi, Shin‐Ichiro NishimuraChemistry – A European Journal 26 54 12363 - 12372 2020年08月28日 [査読有り]
Abstract Human NOTCH1 receptor contains 36 epidermal growth factor (EGF)‐like repeating domains, in which O‐glycosylation status of EGF12 domain regulates the interaction with Notch ligands. Our interest is focused on the effect of specific O‐glycosylation states on the structural behavior of EGF11 and EGF10, because they appeared to affect molecular mechanism in receptor–ligand interactions by inducing some conformational alterations in these domains and/or the regions connecting two domains. To understand the structural impact of various O‐glycosylation patterns on the pivotal EGF‐like repeats 10, 11, and 12, we performed chemical synthesis and NMR studies of site‐specifically O‐glycosylated EGF11 and EGF10. Our strategy enabled us to synthesize four EGF11 and five EGF10 modules. The specific O‐glycosylation states affected in vitro folding of EGF10 more than EGF11, while calcium ion had a larger effect on EGF11 folding. Comprehensive NMR studies shed light on the new type “sugar bridges” crosslinking Thr‐O‐GlcNAc in the consensus sequence C5‐X‐X‐G‐X‐(T/S)‐G‐X‐X‐C6 and an amino acid in the hinge region between the domains, 445Thr‐O‐GlcNAc—IIe451 in domain 11 and 405Thr‐O‐GlcNAc—Gln411 in domain 10, respectively. - Shun Hayakawa, Takahiko Matsushita, Yasuhiro Yokoi, Hajime Wakui, Fayna Garcia-Martin, Hiroshi Hinou, Koji Matsuoka, Kazuhiro Nouso, Toshiya Kamiyama, Akinobu Taketomi, Shin-Ichiro NishimuraBiochemistry 59 12 1221 - 1241 2020年03月10日 [査読有り]
- Kazuki Hammura, Akari Ishikawa, Ravi Kumar H. V., Risho Miyoshi, Yasuhiro Yokoi, Masakazu Tanaka, Hiroshi Hinou, Shin-Ichiro NishimuraACS Medicinal Chemistry Letters 9 9 889 - 894 2018年08月10日 [査読有り]
- Shun Hayakawa, Yasuhiro Yokoi, Hiroshi Hinou, Shin-Ichiro NishimuraBiochemistry 56 33 4379 - 4391 2017年08月09日 [査読有り]
- Naoki Ohyabu, Kiyoshi Kakiya, Yasuhiro Yokoi, Hiroshi Hinou, Shin-Ichiro NishimuraJournal of the American Chemical Society 138 27 8392 - 8395 2016年06月29日 [査読有り]
- Shobith Rangappa, Gerard Artigas, Risho Miyoshi, Yasuhiro Yokoi, Shun Hayakawa, Fayna Garcia-Martin, Hiroshi Hinou, Shin-Ichiro NishimuraMedChemComm 7 6 1102 - 1122 2016年03月30日 [査読有り]
The conformational impact of the clusteredO-glycans strongly influences recognition by antibodies of the cancer-relevant epitope in the MUC1 extracellular tandem repeat domain.
講演・口頭発表等
- エクソソーム模倣ナノ粒子 "ナノソーム" によるがん細胞表面ノイラミニダーゼ-1をターゲットとした新規抗がんナノ医薬 [通常講演]村上賢, 横井康広, 平根望巳, 大瀧みちる, 長堀紀子, 西村紳一郎第10回日本細胞外小胞学会学術集会 2023年10月 ポスター発表
- がん細胞のノイラミニダーゼ1 (シアリダーゼ) を標的とするナノ医薬の創出 [通常講演]村上賢, 神部大貴, 横井康広, 涌井初, 平根望巳, 小出亮介, 大瀧みちる, 西村紳一郎第71回高分子討論会 2022年09月 ポスター発表
- Synthesis of Nanosomal Anticancer Drug Targeting Lysosomal Glycosidase [通常講演]Yasuhiro Yokoi, Daiki Kambe, Shin-Ichiro NishimuraThe 2021 International Chemical Congress of Pacific Basin Societies 2021年12月 ポスター発表
- Dynamic O-glycosylation States Regulate the Conformational Characteristics of Individual Human NOTCH1 EGF Domains [通常講演]Yasuhiro Yokoi, Shin-Ichiro NishimuraThe 2021 International Chemical Congress of Pacific Basin Societies 2021年12月 ポスター発表
- Structural Significance of Dynamic O-glycosylations in Human NOTCH1 EGF Domains [通常講演]Yasuhiro Yokoi, Shin-Ichiro Nishimura7th International Life-Science Symposium 2019年11月 口頭発表（一般）
- Conformational and Functional Impacts of Dynamic O-glycosylation States on Human NOTCH1 EGF Domains [通常講演]Yasuhiro Yokoi, Shin-Ichiro Nishimura25th International Symposium on Glycoconjugates 2019年08月 ポスター発表
- NOTCH1 EGFドメインにおけるO-結合型糖鎖修飾の構造および機能 [通常講演]横井康広, 西村紳一郎日本化学会第97春季年会 2017年03月 口頭発表（一般）
- Synthesis and Structural Analysis of Tau Glycoprotein Fragments [通常講演]Yasuhiro Yokoi, Shun Hayakawa, Hiroshi Hinou, Shin-Ichiro Nishimura15th International Conference on Chiroptical Spectroscopy 2015年09月 ポスター発表
- タウタンパクフラグメントの合成および立体構造解析 [通常講演]横井康広, 早川瞬, 比能洋, 西村紳一郎第64回高分子学会年次大会 2015年05月 ポスター発表
その他活動・業績
- 大瀧みちる, 平根望巳, 村上賢, 涌井初, 西村紳一郎, 横井康広, 長堀紀子 月刊腎臓内科 18 (1) 2023年
- 西村紳一郎, 涌井初, 横井康広 臨床化学 50 (4) 2021年
- 横井康広, 西村紳一郎 日本化学会春季年会講演予稿集(CD-ROM) 97th 2017年
- 横井康広, 早川瞬, 比能洋, 西村紳一郎 高分子学会予稿集(CD-ROM) 64 (1) 2015年