Screening and identification of a non-peptide antagonist for the peptide hormone receptor in Arabidopsis

被引:8
|
作者
Shinohara, Hidefumi [1 ]
Yasue, Naoko [2 ]
Onuki, Tetsuo [3 ]
Kondoh, Yasumitsu [3 ]
Yoshida, Minoru [3 ]
Matsubayashi, Yoshikatsu [1 ]
机构
[1] Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan
[2] Natl Inst Basic Biol, Okazaki, Aichi 4448585, Japan
[3] RIKEN, Ctr Sustainable Resource Sci, Hirosawa 2-1, Wako, Saitama 3510198, Japan
基金
日本学术振兴会;
关键词
SIGNALING PATHWAY; CRYSTAL-STRUCTURE; CELL FATE; KINASE; REVEALS; COMPLEX; SHOOT; CONSTRUCTION; DISCOVERY; BAM1;
D O I
10.1038/s42003-019-0307-8
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Intercellular signaling mediated by peptide hormones and membrane-localized receptor kinases plays crucial roles in plant developmental processes. Because of their diverse functions, agonistic or antagonistic modulation of peptide signaling holds enormous promise for agricultural applications. Here we established a high-throughput screening system using a bead-immobilized receptor kinase and fluorescent-labeled peptide ligand to identify small molecules that bind peptide hormone receptors in competition with natural ligands. We used the Arabidopsis CLE9-BAM1 ligand-receptor pair to screen a library of approximate to 30,000 chemicals and identified NPD12704 as an antagonist for BAM1. NPD12704 also inhibited CLV3 binding to BAM1 but only minimally interfered with CLV3 binding to CLV1, the closest homolog of BAM1, demonstrating preferential receptor specificity. Treatment of clv1-101 mutant seedlings with NPD12704 enhanced the enlarged shoot apical meristem phenotype. Our results provide a technological framework enabling high-throughput identification of small non-peptide chemicals that specifically control receptor kinase-mediated peptide hormone signaling in plants.
引用
收藏
页数:8
相关论文
共 50 条
  • [21] CP-154.526: A potent and selective non-peptide antagonist of the CRF receptor
    Chen, YL
    Braselton, J
    Collins, J
    Costello, D
    Corman, M
    Dunaiskis, A
    Faraci, S
    Heym, J
    Mansbach, R
    Schmidt, A
    Schulz, D
    Seeger, T
    Sprouse, J
    Tingley, D
    Winston, E
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1996, 212 : 195 - MEDI
  • [22] Binding, Thermodynamics, and Selectivity of a Non-peptide Antagonist to the Melanocortin-4 Receptor
    Saleh, Noureldin
    Kleinau, Gunnar
    Heyder, Nicolas
    Clark, Timothy
    Hildebrand, Peter W.
    Scheerer, Patrick
    FRONTIERS IN PHARMACOLOGY, 2018, 9
  • [23] Synthesis of non-peptide drug candidates that antagonize the peptide hormone cholecystokinin
    DiPardo, RM
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1996, 212 : 202 - ORGN
  • [24] Characterization of non-peptide antagonist and peptide agonist binding sites of the NK1 receptor with fluorescent ligands
    Turcatti, G
    Zoffmann, S
    Lowe, JA
    Drozda, SE
    Chassaing, G
    Schwartz, TW
    Chollet, A
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (34) : 21167 - 21175
  • [25] Pentamidine is a specific, non-peptide, GPIIb/IIIa antagonist
    Cox, D
    Aoki, T
    Seki, J
    Motoyama, Y
    Yoshida, K
    THROMBOSIS AND HAEMOSTASIS, 1996, 75 (03) : 503 - 509
  • [26] Non-peptide angiotensin II receptor antagonists
    Takeda Chemical Industries, Ltd, Osaka, Japan
    Yuki Gosei Kagaku Kyokaishi, 9 (802-810):
  • [27] Non-peptide AT2-receptor agonists
    Steckelings, U. Muscha
    Larhed, Mats
    Hallberg, Anders
    Widdop, Robert E.
    Jones, Emma S.
    Wallinder, Charlotta
    Namsolleck, Pawel
    Dahlof, Bjorn
    Unger, Thomas
    CURRENT OPINION IN PHARMACOLOGY, 2011, 11 (02) : 187 - 192
  • [28] Discovery of an orally active non-peptide fibrinogen receptor antagonist based on the hydantoin scaffold
    Stilz, HU
    Guba, W
    Jablonka, B
    Just, M
    Klingler, O
    König, W
    Wehner, V
    Zoller, G
    JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (08) : 1158 - 1176
  • [29] Strategies for the design of non-peptide CCK2 receptor agonist and antagonist ligands
    Kalindjian, S. Barret
    McDonald, Iain M.
    CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2007, 7 (12) : 1195 - 1204
  • [30] Screening of ligand binding on melatonin receptor using non-peptide combinatorial libraries
    Boutin, JA
    Lahaye, C
    Pegurier, C
    Nicolas, JP
    Fauchere, JL
    Langlois, M
    Renard, P
    Delagrange, P
    Canet, E
    JOURNAL OF RECEPTOR AND SIGNAL TRANSDUCTION RESEARCH, 2000, 20 (01): : 105 - 118