Results 101 to 110 of about 107,657 (326)

Molecular dynamics simulations of positively selected codons in FcγRI reveal novel biochemical binding properties

FEBS Open Bio, EarlyView.
Evolutionary analysis across 32 placental mammals identified positive selection at residues H148 and W149 in the immune receptor FcγR1. Ancestral reconstruction combined with molecular dynamics simulations reveals how these mutations may influence receptor structure and dynamics, providing insight into the evolution of antibody recognition and immune ...
David A. Young, Omar Arias‐Gaguancela, Fiona Gibson, Morgan Grainger, Jodie Score, Amit Nathubhai, Mauricio Cafiero, Lee Richard Machado   +7 more
wiley   +1 more source

Heterobiaryl and heterobiaryl ether derived M5 positive allosteric modulators [PDF]

Bioorganic & Medicinal Chemistry Letters, 2010
This Letter describes a chemical lead optimization campaign directed at VU0238429, the first M(5)-preferring positive allosteric modulator (PAM), discovered through analog work around VU0119498, a pan G(q) mAChR M(1), M(3), M(5) PAM. An iterative parallel synthesis approach was employed to incorporate basic heterocycles to improve physiochemical ...
Thomas M, Bridges, J Phillip, Kennedy, Corey R, Hopkins, P Jeffrey, Conn, Craig W, Lindsley   +4 more
openaire   +2 more sources

Oppositely Charged Single Enzyme Nanogels Form Versatile Coacervates for Efficient Enzyme Cascade Catalysis

Advanced Materials, EarlyView.
Oppositely charged single enzyme nanogels (SENs) phase‐separate into bi‐enzymatic coacervate microdroplets, acting as both scaffold and functional units. By tuning SEN ratios, these coacervates create specific microenvironments that enable selective small‐molecule enrichment and efficient intermediate diffusion.
Andoni Rodriguez‐Abetxuko, Nadia A. Erkamp, Neshat Moslehi, Yannick H. A. Leurs, Lars Paffen, Işil Yeşil Gür, Jana Stojanović, Hugo Brasselet, Laura van der Weel, Ulf Hanefeld, Ilja K. Voets, Jan C. M. van Hest   +11 more
wiley   +1 more source

M1 receptor positive allosteric modulators discovery approaches

Trends in Pharmacological Sciences
The development of M1 muscarinic acetylcholine-receptor-positive allosteric modulators has been hindered by their limited cognitive efficacy and cholinergic side effects. We discuss two unique approaches - low intrinsic agonism and low binding cooperativity - that were developed to address these issues and their therapeutic implications.
Takao Mandai, Arthur A. Simen, Antonio Laurenza, Haruhide Kimura   +3 more
openaire   +2 more sources

The mGluR2 Positive Allosteric Modulator, AZD8529, and Cue-Induced Relapse to Alcohol Seeking in Rats

, 2016
Group II metabotropic glutamate receptors (mGluR2 and mGluR3) may control relapse of alcohol seeking, but previously available Group II agonists were unable to discriminate between mGluR2 and mGluR3.
Augier, Eric,, Gaëlle Augier, Russell S Dulman, Markus Heilig, Dulman, Russell S.,, Caroline Rauffenbart, Alan J Cross, Heilig, Markus,, Augier, Gaelle,, Rauffenbart, Caroline,, Cross, Alan J.,, Eric Augier   +11 more
core   +1 more source

Targeting UXS1‐Dependent Glucuronate Detoxification Potentiates Metformin's Anti‐Tumor Efficacy in Lung Adenocarcinoma

Advanced Science, EarlyView.
This study reveals that metformin promotes glucuronic acid metabolism in lung adenocarcinoma by activating UGDH S476 phosphorylation and enhancing the conversion of UDPG to UDPGA based on metabolomics analysis. Through compound virtual screening, it is found that plantainoside targeting UGDH downstream UXS1 leads to UDPGA toxicity accumulation ...
Qihai Sui, Zhencong Chen, Guangyao Shan, Zhengyang Hu, Xing Jin, Jiaqi Liang, Yanjun Yi, Jiacheng Yin, Haochun Shi, Xifei Jiang, Junjie Xi, Zongwu Lin, Cheng Zhan, Fenghao Sun, Wei Jiang   +14 more
wiley   +1 more source

Computational analysis of negative and positive allosteric modulator binding and function in metabotropic glutamate receptor 5 (in)activation

, 2014
Metabotropic glutamate receptors (mGluRs) are high-profile G-protein coupled receptors drug targets because of their involvement in several neurological disease states, and mGluR5 in particular is a subtype whose controlled allosteric modulation, both ...
Dalton, James A. R., Gómez-Santacana, Xavier, Llebaria, Amadeu, Giraldo, Jesús   +3 more
core   +1 more source

Natural Products Inspired Scaffold Diversification Leads to Unnatural Molecular Warhead and Covalent Strategy to Modulating Protein Function through Electrophilic Bromine Transfer

Advanced Science, EarlyView.
We report a new thiolate‐reactive α,α‐gem‐dibromo lactam warhead that activates transcription factor Nrf2 and demonstrates anti‐inflammatory activities, which have implications in cancer, neurodegeneration, and cardiovascular diseases. RNA‐seq illuminated detailed transcriptional profiles, and chemical reactions with cysteine‐containing compounds ...
Beau R. Brummel, Sofia Kokkaliari, Qiwen Gao, Jinjing Chen, Larissa Costa de Almeida, Srinivasarao Tenneti, Derek A. Leas, Eli Levit, Lewis S. Alexander, Khalil A. Abboud, Pingrong Wei, Michael D. Cameron, James R. Rocca, Ranjala Ratnayake, Donna D. Zhang, Hendrik Luesch, Robert W. Huigens III   +16 more
wiley   +1 more source

Allosteric modulation of Ras positions Q61 for a direct role in catalysis [PDF]

Proceedings of the National Academy of Sciences, 2010
Ras and its effector Raf are key mediators of the Ras/Raf/MEK/ERK signal transduction pathway. Mutants of residue Q61 impair the GTPase activity of Ras and are found prominently in human cancers. Yet the mechanism through which Q61 contributes to catalysis has been elusive. It is thought to position the catalytic water molecule for
Greg, Buhrman, Genevieve, Holzapfel, Susan, Fetics, Carla, Mattos   +3 more
openaire   +2 more sources

Computational Analysis of Negative and Positive Allosteric Modulator Binding and Function in Metabotropic Glutamate Receptor 5 (In)Activation

, 2016
Metabotropic glutamate receptors (mGluRs) are high-profile G-protein coupled receptors drug targets because of their involvement in several neurological disease states, and mGluR5 in particular is a subtype whose controlled allosteric modulation, both ...
Xavier Gómez-Santacana (2106892), Amadeu Llebaria (1626844), Jesús Giraldo (1558987), James A. R. Dalton (2106895)   +3 more
core   +1 more source