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Your search keyword '"Shanliang Sun"' showing total 3 results
Start Over Author "Shanliang Sun" Topic chemokine receptor
3 results on '"Shanliang Sun"'

1. A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

Author

Xavier Gómez-Santacana, Sabrina M. de Munnik, Tamara A. M. Mocking, Niels J. Hauwert, Shanliang Sun, Prashanna Vijayachandran, Iwan J. P. de Esch, Henry F. Vischer, Maikel Wijtmans, and Rob Leurs

Subjects
azo compounds, chemokine receptor, efficacy photoswitching, g protein-coupled receptors, photopharmacology, Science, Organic chemistry, QD241-441
Abstract

We report a detailed structure–activity relationship for the scaffold of VUF16216, a compound we have previously communicated as a small-molecule efficacy photoswitch for the peptidergic chemokine GPCR CXCR3. A series of photoswitchable azobenzene ligands was prepared through various synthetic strategies and multistep syntheses. Photochemical and pharmacological properties were used to guide the design iterations. Investigations of positional and substituent effects reveal that halogen substituents on the ortho-position of the outer ring are preferred for conferring partial agonism on the cis form of the ligands. This effect could be expanded by an electron-donating group on the para-position of the central ring. A variety of efficacy differences between the trans and cis forms emerges from these compounds. Tool compounds VUF15888 (4d) and VUF16620 (6e) represent more subtle efficacy switches, while VUF16216 (6f) displays the largest efficacy switch, from antagonism to full agonism. The compound class disclosed here can aid in new photopharmacology studies of CXCR3 signaling.

Published
2019
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2. Structure-based exploration and pharmacological evaluation of N-substituted piperidin-4-yl-methanamine CXCR4 chemokine receptor antagonists

Author

I.J.P. de Esch, Rob Leurs, Stephen J. Hill, M. Gozelle, Marta Arimont, Henry F. Vischer, Birgit Caspar, Aurélien Zarca, Ilze Adlere, Luc Roumen, Stephen J. Briddon, Maikel Wijtmans, Martine J. Smit, Shanliang Sun, C. Perpiñá Viciano, J.P. Bebelman, Carsten Hoffmann, C de Graaf, Medicinal chemistry, AIMMS, and Chemistry and Pharmaceutical Sciences

Subjects
Models, Molecular, Receptors, CXCR4, Stereochemistry, Quantitative Structure-Activity Relationship, Ligands, 01 natural sciences, CXCR4, Hydrophobic effect, Methylamines, 03 medical and health sciences, Chemokine receptor, CXCR4 chemokine receptor, Piperidines, G protein-coupled receptors, SDG 3 - Good Health and Well-being, Drug Discovery, Structure–activity relationship, Binding site, 030304 developmental biology, G protein-coupled receptor, 3D-QSAR, Pharmacology, 0303 health sciences, Virtual screening, Binding Sites, 010405 organic chemistry, Chemistry, Organic Chemistry, General Medicine, Ligand (biochemistry), Structure-activity relationship, Chemokine CXCL12, Peptide Fragments, Structure-based fragment virtual screening, 0104 chemical sciences, Antagonists, Protein Binding
Abstract

Using the available structural information of the chemokine receptor CXCR4, we present hit finding and hit exploration studies that make use of virtual fragment screening, design, synthesis and structure activity relationship (SAR) studies. Fragment 2 was identified as virtual screening hit and used as a starting point for the exploration of 31 N-substituted piperidin-4-yl-methanamine derivatives to investigate and improve the interactions with the CXCR4 binding site. Additionally, subtle structural ligand changes lead to distinct interactions with CXCR4 resulting in a full to partial displacement of CXCL12 binding and competitive and/or non-competitive antagonism. Three-dimensional quantitative structure-activity relationship (3D-QSAR) and binding model studies were used to identify important hydrophobic interactions that determine binding affinity and indicate key ligand-receptor interactions. (C) 2018 Elsevier Masson SAS. All rights reserved.

Published
2019
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3. Structural Analysis of Chemokine Receptor-Ligand Interactions

Author

Chris de Graaf, Rob Leurs, Marta Arimont, Martine J. Smit, Iwan J. P. de Esch, and Shanliang Sun

Subjects
0301 basic medicine, Models, Molecular, CCR2, Chemokine, Receptors, CXCR4, Receptors, CCR5, Stereochemistry, Protein Conformation, Receptors, CCR2, CCR9, Computational biology, Crystallography, X-Ray, Ligands, CXCR4, 03 medical and health sciences, Chemokine receptor, Structure-Activity Relationship, Drug Discovery, Journal Article, Humans, Computer Simulation, Binding site, Receptor, Binding Sites, biology, Chemistry, Ligand (biochemistry), 030104 developmental biology, Perspective, biology.protein, Mutagenesis, Site-Directed, Molecular Medicine, Receptors, Chemokine
Abstract

This review focuses on the construction and application of structural chemokine receptor models for the elucidation of molecular determinants of chemokine receptor modulation and the structure-based discovery and design of chemokine receptor ligands. A comparative analysis of ligand binding pockets in chemokine receptors is presented, including a detailed description of the CXCR4, CCR2, CCR5, CCR9, and US28 X-ray structures, and their implication for modeling molecular interactions of chemokine receptors with small-molecule ligands, peptide ligands, and large antibodies and chemokines. These studies demonstrate how the integration of new structural information on chemokine receptors with extensive structure-activity relationship and site-directed mutagenesis data facilitates the prediction of the structure of chemokine receptor-ligand complexes that have not been crystallized. Finally, a review of structure-based ligand discovery and design studies based on chemokine receptor crystal structures and homology models illustrates the possibilities and challenges to find novel ligands for chemokine receptors.

Published
2017
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