Literature DB >> 24997604

A potentiator of orthosteric ligand activity at GLP-1R acts via covalent modification.

Whitney M Nolte1, Jean-Philippe Fortin2, Benjamin D Stevens1, Gary E Aspnes3, David A Griffith1, Lise R Hoth4, Roger B Ruggeri1, Alan M Mathiowetz1, Chris Limberakis3, David Hepworth1, Philip A Carpino1.   

Abstract

We report that 4-(3-(benzyloxy)phenyl)-2-ethylsulfinyl-6-(trifluoromethyl)pyrimidine (BETP), which behaves as a positive allosteric modulator at the glucagon-like peptide-1 receptor (GLP-1R), covalently modifies cysteines 347 and 438 in GLP-1R. C347, located in intracellular loop 3 of GLP-1R, is critical to the activity of BETP and a structurally distinct GLP-1R ago-allosteric modulator, N-(tert-butyl)-6,7-dichloro-3-(methylsulfonyl)quinoxalin-2-amine. We further show that substitution of cysteine for phenylalanine 345 in the glucagon receptor is sufficient to confer sensitivity to BETP.

Entities:  

Mesh：

Substances：

Year:  2014        PMID： 24997604     DOI： 10.1038/nchembio.1581

Source DB:  PubMed          Journal:  Nat Chem Biol        ISSN： 1552-4450            Impact factor:   15.040


  21 in total

1.  Allosteric ligands of the glucagon-like peptide 1 receptor (GLP-1R) differentially modulate endogenous and exogenous peptide responses in a pathway-selective manner: implications for drug screening.

Authors:  Cassandra Koole; Denise Wootten; John Simms; Celine Valant; Rohan Sridhar; Owen L Woodman; Laurence J Miller; Roger J Summers; Arthur Christopoulos; Patrick M Sexton
Journal:  Mol Pharmacol       Date:  2010-06-14       Impact factor: 4.436

2.  Small molecule allosteric modulation of the glucagon-like Peptide-1 receptor enhances the insulinotropic effect of oxyntomodulin.

Authors:  Francis S Willard; Denise Wootten; Aaron D Showalter; Emilia E Savage; James Ficorilli; Thomas B Farb; Krister Bokvist; Jorge Alsina-Fernandez; Sebastian G B Furness; Arthur Christopoulos; Patrick M Sexton; Kyle W Sloop
Journal:  Mol Pharmacol       Date:  2012-08-28       Impact factor: 4.436

3.  Dipeptidyl peptidase IV (DPIV/CD26) degradation of glucagon. Characterization of glucagon degradation products and DPIV-resistant analogs.

Authors:  S A Hinke; J A Pospisilik; H U Demuth; S Mannhart; K Kühn-Wache; T Hoffmann; E Nishimura; R A Pederson; C H McIntosh
Journal:  J Biol Chem       Date:  2000-02-11       Impact factor: 5.157

4.  Scanning of the glucagon-like peptide-1 receptor localizes G protein-activating determinants primarily to the N terminus of the third intracellular loop.

Authors:  S K Mathi; Y Chan; X Li; M B Wheeler
Journal:  Mol Endocrinol       Date:  1997-04

Review 5.  Clinical endocrinology and metabolism. Glucagon-like peptide-1 and glucagon-like peptide-2.

Authors:  Laurie L Baggio; Daniel J Drucker
Journal:  Best Pract Res Clin Endocrinol Metab       Date:  2004-12       Impact factor: 4.690

6.  Differential activation and modulation of the glucagon-like peptide-1 receptor by small molecule ligands.

Authors:  Denise Wootten; Emilia E Savage; Francis S Willard; Ana B Bueno; Kyle W Sloop; Arthur Christopoulos; Patrick M Sexton
Journal:  Mol Pharmacol       Date:  2013-01-24       Impact factor: 4.436

7.  GLP-1 mediates antiapoptotic effect by phosphorylating Bad through a beta-arrestin 1-mediated ERK1/2 activation in pancreatic beta-cells.

Authors:  Julie Quoyer; Christine Longuet; Christophe Broca; Nathalie Linck; Safia Costes; Elodie Varin; Joël Bockaert; Gyslaine Bertrand; Stéphane Dalle
Journal:  J Biol Chem       Date:  2009-11-13       Impact factor: 5.157

8.  Allosteric modulation of endogenous metabolites as an avenue for drug discovery.

Authors:  Denise Wootten; Emilia E Savage; Celine Valant; Lauren T May; Kyle W Sloop; James Ficorilli; Aaron D Showalter; Francis S Willard; Arthur Christopoulos; Patrick M Sexton
Journal:  Mol Pharmacol       Date:  2012-05-10       Impact factor: 4.436

9.  Novel small molecule glucagon-like peptide-1 receptor agonist stimulates insulin secretion in rodents and from human islets.

Authors:  Kyle W Sloop; Francis S Willard; Martin B Brenner; James Ficorilli; Kathleen Valasek; Aaron D Showalter; Thomas B Farb; Julia X C Cao; Amy L Cox; M Dodson Michael; Sonia Maria Gutierrez Sanfeliciano; Mark J Tebbe; Michael J Coghlan
Journal:  Diabetes       Date:  2010-09-07       Impact factor: 9.461

Review 10.  Physiology and emerging biochemistry of the glucagon-like peptide-1 receptor.

Authors:  Francis S Willard; Kyle W Sloop
Journal:  Exp Diabetes Res       Date:  2012-05-14
View more
  26 in total

Review 1.  Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes.

Authors:  Chris de Graaf; Dan Donnelly; Denise Wootten; Jesper Lau; Patrick M Sexton; Laurence J Miller; Jung-Mo Ahn; Jiayu Liao; Madeleine M Fletcher; Dehua Yang; Alastair J H Brown; Caihong Zhou; Jiejie Deng; Ming-Wei Wang
Journal:  Pharmacol Rev       Date:  2016-10       Impact factor: 25.468

Review 2.  Novel Allosteric Modulators of G Protein-coupled Receptors.

Authors:  Patrick R Gentry; Patrick M Sexton; Arthur Christopoulos
Journal:  J Biol Chem       Date:  2015-06-22       Impact factor: 5.157

3.  Allostery: A GPCR's back door.

Authors:  Klaus Mohr; Evi Kostenis
Journal:  Nat Chem Biol       Date:  2014-08       Impact factor: 15.040

4.  Structural biology: Full monty of family B GPCRs.

Authors:  Thue W Schwartz; Thomas M Frimurer
Journal:  Nat Chem Biol       Date:  2017-07-18       Impact factor: 15.040

5.  Activation of the GLP-1 receptor by a non-peptidic agonist.

Authors:  Peishen Zhao; Yi-Lynn Liang; Matthew J Belousoff; Giuseppe Deganutti; Madeleine M Fletcher; Francis S Willard; Michael G Bell; Michael E Christe; Kyle W Sloop; Asuka Inoue; Tin T Truong; Lachlan Clydesdale; Sebastian G B Furness; Arthur Christopoulos; Ming-Wei Wang; Laurence J Miller; Christopher A Reynolds; Radostin Danev; Patrick M Sexton; Denise Wootten
Journal:  Nature       Date:  2020-01-08       Impact factor: 49.962

Review 6.  Structural Basis for Allosteric Modulation of Class B G Protein-Coupled Receptors.

Authors:  Denise Wootten; Laurence J Miller
Journal:  Annu Rev Pharmacol Toxicol       Date:  2019-08-27       Impact factor: 13.820

7.  Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators.

Authors:  Gaojie Song; Dehua Yang; Yuxia Wang; Chris de Graaf; Qingtong Zhou; Shanshan Jiang; Kaiwen Liu; Xiaoqing Cai; Antao Dai; Guangyao Lin; Dongsheng Liu; Fan Wu; Yiran Wu; Suwen Zhao; Li Ye; Gye Won Han; Jesper Lau; Beili Wu; Michael A Hanson; Zhi-Jie Liu; Ming-Wei Wang; Raymond C Stevens
Journal:  Nature       Date:  2017-05-17       Impact factor: 49.962

8.  Use of Cysteine Trapping to Map Spatial Approximations between Residues Contributing to the Helix N-capping Motif of Secretin and Distinct Residues within Each of the Extracellular Loops of Its Receptor.

Authors:  Maoqing Dong; Polo C-H Lam; Andrew Orry; Patrick M Sexton; Arthur Christopoulos; Ruben Abagyan; Laurence J Miller
Journal:  J Biol Chem       Date:  2016-01-06       Impact factor: 5.157

9.  Isolation of Positive Modulator of Glucagon-like Peptide-1 Signaling from Trigonella foenum-graecum (Fenugreek) Seed.

Authors:  Klim King; Nai-Pin Lin; Yu-Hong Cheng; Gao-Hui Chen; Rong-Jie Chein
Journal:  J Biol Chem       Date:  2015-09-02       Impact factor: 5.157

Review 10.  New paradigms in GPCR drug discovery.

Authors:  Kenneth A Jacobson
Journal:  Biochem Pharmacol       Date:  2015-08-08       Impact factor: 5.858
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.