Protein-recruiting synthetic molecules targeting the Golgi surface

2020 ◽  
Vol 56 (98) ◽  
pp. 15422-15425
Author(s):  
Shunsuke Sawada ◽  
Akinobu Nakamura ◽  
Tatsuyuki Yoshii ◽  
Keiko Kuwata ◽  
Fubito Nakatsu ◽  
...  
Keyword(s):  
Small Molecule ◽  
Living Cells ◽  
Target Proteins ◽  
Synthetic Molecules ◽  
Chemical Tools ◽  
Small Molecule Ligand

Synthetic molecules consisting of a small-molecule ligand and a tri-N-methylated myristoyl-Gly-Cys lipopeptide serve as chemical tools to rapidly recruit their target proteins from the cytoplasm to the Golgi surface in living cells.

Golgi recruitment assay for visualizing small-molecule ligand–target engagement in cells

2020 ◽  
Vol 56 (57) ◽  
pp. 7961-7964
Author(s):  
Sachio Suzuki ◽  
Masahiro Ikuta ◽  
Tatsuyuki Yoshii ◽  
Akinobu Nakamura ◽  
Keiko Kuwata ◽  
...  
Keyword(s):  
Small Molecule ◽  
Living Cells ◽  
New Method ◽  
Target Engagement ◽  
Small Molecule Ligand ◽  
In Cells

A Golgi recruitment (G-REC) assay is developed as a new method for visualizing small-molecule ligand–target engagement in living cells.

Recent advances in 1,8-naphthalimide-based small-molecule fluorescent probes for organelles imaging and tracking in living cells

2021 ◽  
Vol 444 ◽  
pp. 214019
Author(s):  
Haitao Yu ◽  
Yan Guo ◽  
Wencheng Zhu ◽  
Kaden Havener ◽  
Xujun Zheng
Keyword(s):  
Small Molecule ◽  
Fluorescent Probes ◽  
Living Cells ◽  
Recent Advances

Small-molecule FRET probes for protein kinase activity monitoring in living cells

2010 ◽  
Vol 397 (4) ◽  
pp. 750-755 ◽  
Author(s):  
Angela Vaasa ◽  
Marje Lust ◽  
Anna Terrin ◽  
Asko Uri ◽  
Manuela Zaccolo
Keyword(s):  
Protein Kinase ◽  
Small Molecule ◽  
Kinase Activity ◽  
Living Cells ◽  
Activity Monitoring ◽  
Protein Kinase Activity

Small-molecule degraders of cyclin-dependent kinase protein: a review

2021 ◽  
Author(s):  
Bin Yu ◽  
Zekun Du ◽  
Yuming Zhang ◽  
Zhiyu Li ◽  
Jinlei Bian
Keyword(s):  
Cell Cycle ◽  
Drug Resistance ◽  
Protein Degradation ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Structural Characteristics ◽  
Protein A ◽  
Cyclin Dependent Kinase ◽  
Chemical Tools ◽  
Potential Therapeutics

Proteolysis-targeting chimeras are a new modality of chemical tools and potential therapeutics involving the induction of protein degradation. Cyclin-dependent kinase (CDK) protein, which is involved in cycles and transcription cycles, participates in regulation of the cell cycle, transcription and splicing. Proteolysis-targeting chimeras targeting CDKs show several advantages over traditional CDK small-molecule inhibitors in potency, selectivity and drug resistance. In addition, the discovery of molecule glues promotes the development of CDK degraders. Herein, the authors describe the existing CDK degraders and focus on the discussion of the structural characteristics and design of these degraders.

On the propagation of errors

2013 ◽  
Vol 69 (10) ◽  
pp. 1865-1866 ◽  
Author(s):  
Mariusz Jaskolski
Keyword(s):  
Protein Data Bank ◽  
Small Molecule ◽  
Data Bank ◽  
Propagation Of Errors ◽  
Small Molecule Ligand

The policy of the Protein Data Bank (PDB) that the first deposition of a small-molecule ligand, even with erroneous atom numbering, sets a precedent over accepted nomenclature rules is disputed. Recommendations regarding ligand molecules in the PDB are suggested.

Validation and Development of an Escherichia coli Riboflavin Pathway Phenotypic Screen Hit as a Small-Molecule Ligand of the Flavin Mononucleotide Riboswitch

2018 ◽  
pp. 19-40
Author(s):  
Carl J. Balibar ◽  
Artjohn Villafania ◽  
Christopher M. Barbieri ◽  
Nick Murgolo ◽  
Terry Roemer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Small Molecule ◽  
Flavin Mononucleotide ◽  
Phenotypic Screen ◽  
Small Molecule Ligand

scholarly journals Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine

2014 ◽  
Vol 57 (22) ◽  
pp. 9693-9699 ◽  
Author(s):  
Emmanuel W. Smith ◽  
Yan Liu ◽  
Anthony E. Getschman ◽  
Francis C. Peterson ◽  
Joshua J. Ziarek ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Small Molecule ◽  
Small Molecule Ligand

scholarly journals Development of a hydrolysis-based small-molecule hydrogen selenide (H2Se) donor

2019 ◽  
Vol 10 (46) ◽  
pp. 10723-10727 ◽  
Author(s):  
Turner D. Newton ◽  
Michael D. Pluth
Keyword(s):  
Small Molecule ◽  
Hydrogen Selenide ◽  
Chemical Tools

Hydrolysis-based H2Se donors provide new chemical tools for investigating biological H2Se.

scholarly journals Allosteric “beta-blocker” isolated from a DNA-encoded small molecule library

2017 ◽  
Vol 114 (7) ◽  
pp. 1708-1713 ◽  
Author(s):  
Seungkirl Ahn ◽  
Alem W. Kahsai ◽  
Biswaranjan Pani ◽  
Qin-Ting Wang ◽  
Shuai Zhao ◽  
...  
Keyword(s):  
Binding Site ◽  
G Protein ◽  
Small Molecule ◽  
Adrenergic Receptor ◽  
Camp Production ◽  
Small Molecule Library ◽  
Small Molecule Libraries ◽  
Negative Allosteric Modulator ◽  
G Protein Coupled ◽  
Small Molecule Ligand

The β2-adrenergic receptor (β2AR) has been a model system for understanding regulatory mechanisms of G-protein–coupled receptor (GPCR) actions and plays a significant role in cardiovascular and pulmonary diseases. Because all known β-adrenergic receptor drugs target the orthosteric binding site of the receptor, we set out to isolate allosteric ligands for this receptor by panning DNA-encoded small-molecule libraries comprising 190 million distinct compounds against purified human β2AR. Here, we report the discovery of a small-molecule negative allosteric modulator (antagonist), compound 15 [([4-((2S)-3-(((S)-3-(3-bromophenyl)-1-(methylamino)-1-oxopropan-2-yl)amino)-2-(2-cyclohexyl-2-phenylacetamido)-3-oxopropyl)benzamide], exhibiting a unique chemotype and low micromolar affinity for the β2AR. Binding of 15 to the receptor cooperatively enhances orthosteric inverse agonist binding while negatively modulating binding of orthosteric agonists. Studies with a specific antibody that binds to an intracellular region of the β2AR suggest that 15 binds in proximity to the G-protein binding site on the cytosolic surface of the β2AR. In cell-signaling studies, 15 inhibits cAMP production through the β2AR, but not that mediated by other Gs-coupled receptors. Compound 15 also similarly inhibits β-arrestin recruitment to the activated β2AR. This study presents an allosteric small-molecule ligand for the β2AR and introduces a broadly applicable method for screening DNA-encoded small-molecule libraries against purified GPCR targets. Importantly, such an approach could facilitate the discovery of GPCR drugs with tailored allosteric effects.

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