scholarly journals Evaluation of fully-functionalized diazirine tags for chemical proteomic applications

2021 ◽  
Author(s):  
Louis P. Conway ◽  
Appaso M. Jadhav ◽  
Rick A. Homan ◽  
Weichao Li ◽  
Juanita Sanchez Rubiano ◽  
...  
Keyword(s):  
Photoaffinity Probes

The chemical proteomic properties of five diazirine-based, fully-functionalized photoaffinity tags, including a newly developed, minimal tag, were compared. This study provides guidance for the development of new photoaffinity probes.

One‐Step Synthesis of Photoaffinity Probes for Live‐Cell MS‐Based Proteomics

2021 ◽  
Author(s):  
David J. Fallon ◽  
Stephanie Lehmann ◽  
Chun-wa Chung ◽  
Alex Phillipou ◽  
H. Christian Eberl ◽  
...  
Keyword(s):  
Live Cell ◽  
Photoaffinity Probes ◽  
One Step

scholarly journals Xanthine-Based Photoaffinity Probes Allow Assessment of Ligand Engagement by TRPC5 Channels

2020 ◽  
Author(s):  
Claudia Bauer ◽  
Aisling Minard ◽  
Isabelle Pickles ◽  
Matthew Burnham ◽  
Nikil Kapur ◽  
...  
Keyword(s):  
Small Molecule ◽  
Drug Targets ◽  
Direct Evidence ◽  
Binding Mode ◽  
Chemical Probes ◽  
Binding Interaction ◽  
Biological Studies ◽  
Photoaffinity Probes ◽  
Direct Binding ◽  
Trpc5 Channels

TRPC1/4/5 cation channels are emerging drug targets for the treatment of, amongst others, central nervous system (CNS) disorders, kidney disease, and cardiovascular and metabolic disease. Various small-molecule TRPC1/4/5 modulators have been reported, including highly potent xanthine derivatives that can distinguish between specific TRPC1/4/5 tetramers. However, there is a paucity of information about their binding mode, which limits the ability to develop them further as chemical probes of specific TRPC1/4/5 channels for use in fundamental biological studies and drug discovery programmes. Here, we report the development of a set of potent xanthine-based photoaffinity probes that functionally mimic the xanthines Pico145 and AM237, respectively. Using these probes, we have developed a quantitative photoaffinity labelling protocol for TRPC5 channels. Our results provide the first direct evidence that xanthines modulate TRPC5 channels through a direct binding interaction with TRPC5 protein, and the first quantitative method for the assessment of binding interactions of TRPC5 and small molecules. Our method may allow the study of the mode-of-action of other TRPC1/4/5 modulators, and the identification of small molecule binding sites of TRPC1/4/5 channels.

O1-11-01: Gamma-secretase inhibitor (GSI) and modulator (GSM) photoaffinity probes reveal distinct binding sites on presenilin

2013 ◽  
Vol 9 ◽  
pp. P151-P151
Author(s):  
Doug Johnson ◽  
Kelly Bales ◽  
Nikolay Pozdnyakov ◽  
Heather Murrey ◽  
Martin Pettersson ◽  
...  
Keyword(s):  
Binding Sites ◽  
Gamma Secretase ◽  
Secretase Inhibitor ◽  
Photoaffinity Probes ◽  
Gamma Secretase Inhibitor
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