Leland Stanford Junior University

Vrije Universiteit Brussel

Vib Vzw

University of California

Wisconsin Alumni Research Foundation

Friedrich-Alexander-Universitat Erlangen-Nürnberg

University of Michigan

The University of North Carolina at Chapel Hill

Confometrx, Inc.

Cornell University

Heptares Therapeutics Limited

Brian K Kobilka

Toon Laeremans

Jan Steyaert

Els Pardon

Soren G F Rasmussen

Daniel M Rosenbaum

Juan Jose Fung

Aashish Manglik

Samuel Helmer Gellman

Pil Seok Chae

Roger K Sunahara

Peter Gmeiner

Soren Rasmussen

Aaron Michael Ring

Brian K Shoichet

Andrew Curtis Kruse

Daniela Gisela Dengler

Bryan Leo Roth

Yaozhong Zou

Henry Lin

Sebastien Granier

Peter Brams

Scott C Blanchard

Aaron J Hsueh

Asna Masood

Tae Weon Lee

Harald Huebner

Anat Levit

Masataka Kudo

Luis Maul

Gabriel Glenn Gregorio

Mary Joyce Clark

Anne Stößel

Dorothée Möller

Markus Stanek

Jeremy Shonberg

Harald Hübner

Gebhard F X Schertler

Dan Rohrer

Michael Bokoch

Soren Rasumssen

Sebastian Granier

Søren Rasmussen

Aasish Manglik

Sébastien Granier

The present disclosure relates to the field of G protein coupled receptor (GPCR) structural biology and signaling. In particular, the present disclosure relates to binding domains directed against and/or specifically binding to GPCR:G protein complexes. Also provided are nucleic acid sequences encoding such binding domains and cells expressing or capable of expressing such binding domains. The binding domains of the present disclosure can be used as universal tools for the structural and functional characterization of G-protein coupled receptors in complex with downstream heterotrimeric G proteins and bound to various natural or synthetic ligands, for investigating the dynamic features of G protein activation, as well as for screening and drug discovery efforts that make use of GPCR:G protein complexes.

Binding domains directed against GPCR:G protein complexes and uses derived thereof

The present invention relates to the field of GPCR structure biology and signaling. In particular, the present invention relates to protein binding domains directed against or capable of specifically binding to a functional conformational state of a G-protein-coupled receptor (GPCR). More specifically, the present invention provides protein binding domains that are capable of increasing the stability of a functional conformational state of a GPCR, in particular, increasing the stability of a GPCR in its active conformational state. The protein binding domains of the present invention can be used as a tool for the structural and functional characterization of G-protein-coupled receptors bound to various natural and synthetic ligands, as well as for screening and drug discovery efforts targeting GPCRs. Moreover, the invention also encompasses the diagnostic, prognostic and therapeutic usefulness of these protein binding domains for GPCR-related diseases.

Protein binding domains stabilizing functional conformational states of GPCRS and uses thereof

Disclosed herein are methods for providing a molecular efficacy of a ligand, especially when utilizing single-molecule fluorescence resonance energy transfer ('smFRET') imaging, as well as compounds useful in such methods.

Methods for quantifying ligand efficacy in G-protein coupled receptors using single-molecule fluorescence energy transfer

Aspects of the present disclosure include conformationally restricted analogs of catecholamine type compounds (e.g., isoprenaline, adrenaline, noradrenaline) which activate &#x3b2;2AR with high selectivity over &#x3b2;1AR. The subject beta-2 selective adrenergic receptor agonist compounds may serve as bronchiodilators and find use in the treatment of a variety of bronchoconstrictive diseases and conditions. Also provided are compositions and methods for treating preterm labor. A method of treating acute asthma including administration of a subject compound to a subject in need thereof is provided. The subject method can provide for reduced undesirable side effects associated with non-selective &#x3b2;-adrenergic receptor agonism, such as inotropic and chronotropic effects that leads to elevated blood pressure. The compounds can also be used to prevent or treat heart failure. Kits and compositions for practicing the subject methods are also provided.

Beta-2 selective adrenergic receptor agonists

Described herein, inter alia, are compositions and methods for modulating mu opioid receptor activity.

Mu opioid receptor modulators

Agents that specifically bind to an opioid receptor in a conformationally specific way can be used to induce a conformational change in the receptor. Such agents have therapeutic applications and can be used in X-ray crystallography studies of the receptor. Such agents can also be used to improve drug discovery via compound screening and/or structure-based drug design.

Opioid receptor binding agents and uses thereof

Protein binding domains stabilizing functional conformational states of GPCRs and uses thereof

Provided herein are several methods for selecting agents that bind to transmembrane receptors in a conformationally-selective way. In some embodiments, the method may comprise producing: a transmembrane receptor in an active conformation; and said transmembrane receptor in an inactive conformation and using cell sorting to select, from a population of cells comprising a library of cell surface-tethered extracellular capture agents, cells that are specifically bound to either the transmembrane receptor in its active conformation or the transmembrane receptor in its inactive conformation, but not both. In other embodiments, the method may comprise: contacting a GPCR with a population of cells that comprise a library of surface-tethered extracellular proteins; labeling the cell population with a conformationally-specific binding agent, e.g., a G-protein or mimetic thereof; and using cell sorting to select from the cell population cells that bind to the agent.

Compositions comprising G protein-coupled receptors maintained in a conformationally selective manner by a modulator

MU opioid receptor modulators

Complexes comprising transmembrane receptors and antibodies that bind the receptors in a conformationally selective manner

Growing community of inventors

Stanford, CA, United States of America

Brian K Kobilka