A photoaffinity probe that targets folate-binding proteins

Takamura, Akihiro; Thuy‐Boun, Peter S.; Kitamura, Seiya; Han, Zhigang; Wolan, Dennis W.

doi:10.1016/j.bmcl.2021.127903

Cited by 4 publications

(3 citation statements)

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“…[113] Furthermore, proteomic analysis identified other proteins that both probes labeled, as well as enzymes for which these B vitamins may be a cofactor. [113] Other photoaffinity probes for folate (Folate-photoclick, Figure 11) [114] and sialic acid (Sialic-photoclick, Figure 11) [115] have been developed and identified bacterial protein binding partners in E. coli and murine gut microbiome isolates, respectively. This strategy has also been applied to identify the cellular targets of the antibacterial natural product, promysalin [116] and cajaninstilbene acid.…”

Section: Metabolite-protein Interactionsmentioning

confidence: 99%

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Chemoproteomic Approaches for Unraveling Prokaryotic Biology

Malarney

Chang

2023

Israel Journal of Chemistry

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Bacteria are ubiquitous lifeforms with important roles in the environment, biotechnology, and human health. Many of the functions that bacteria perform are mediated by proteins and enzymes, which catalyze metabolic transformations of small molecules and modifications of proteins. To better understand these biological processes, chemical proteomic approaches, including activity-based protein profiling, have been developed to interrogate protein function and enzymatic activity in physiologically relevant contexts. Here, chemoproteomic strategies and technological advances for studying bacterial physiology, pathogenesis, and metabolism are discussed. The development of chemoproteomic approaches for characterizing protein function and enzymatic activity within bacteria remains an active area of research, and continued innovations are expected to provide breakthroughs in understanding bacterial biology.

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Section: Metabolite-protein Interactionsmentioning

confidence: 99%

“…[118] Further-Figure 11. Photoaffinity probes used to identify metabolite-protein interactions [113][114][115]118] with click chemistry handles (blue) and reactive photocrosslinkers (pink) indicated.…”

Section: Metabolite-protein Interactionsmentioning

confidence: 99%

Chemoproteomic Approaches for Unraveling Prokaryotic Biology

Malarney

Chang

2023

Israel Journal of Chemistry

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“…Numerous innovative methods including thermal protein profiling (TPP) 1 , limited proteolysis (LiP) [2][3][4] , stability of proteins from rates of oxidation (SPROX) 5 , covalent protein painting (CPP) 6 , and photoaffinity labeling (PAL) [7][8][9][10][11] have yielded proteome-wide portraits of protein-protein [12][13][14] , proteinoligonucleotide 15 , protein-lipid [16][17][18][19][20][21][22] , protein-metabolite 23 , protein-natural products [24][25][26][27] , proteinglycan 28 , protein-cofactor [16][17][18] , protein-small molecule 10,11,29 , and even protein-drug interactions [30][31][32][33][34] .…”

Section: Introductionmentioning

confidence: 99%

Silyl Ether Enables High Coverage Chemoproteomic Interaction Site Mapping

Takechi,

Ngo,

Burton

et al. 2024

Preprint

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Most therapeutics are small molecules that function by interacting with specific protein targets. Consequently, delineating the protein targets, including the specific binding sites, for chemical probes and clinical candidates is essential to ensure potent on-target activity and to minimize engagement of unfavorable off-targets. The pairing of mass spectrometry-based chemoproteomics with photoaffinity labeling (PAL) has emerged as a favored approach to generate proteome-wide target engagement maps for reversible compounds. However, a key limitation of most PAL-based proteomic platforms is the absence of strategies that report precise binding sites and enable direct head-to-head comparisons of relative target engagement at these sites by different lead compounds. This gap stems from a confluence of factors including the complex fragmentation patterns for crosslinked peptides, poor recovery of peptides crosslinked with large hydrophobic molecules, and modification masses that differ between molecules of interest (MOI). To address these challenges, here we establish the Silyl Ether Enables Chemoproteomic Interaction and Target Engagement (SEE-CITE) approach. SEE-CITE incorporates an unprecedented fully functionalized chemically cleavable crosslinking handle that enables precise site-of-labeling identification and head-to-head comparisons of relative binding site engagement by chemically diverse compounds. To ensure high confidence localization of labeled residues, we also enabled enhanced mapping of photocrosslinked sites by extending the MSFragger algorithm of the FragPipe computational platform to report localization scores customized for PAL and SEE-CITE data. By benchmarking SEE-CITE using scout fragments and analogues of the FDA-approved kinase inhibitors dasatinib and asciminib, we identify known and novel binding sites, including for high impact targets, such as BCR-ABL1, STING, and COX5A.

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Activity-based protein profiling in microbes and the gut microbiome

Lin

Chang

2023

Current Opinion in Chemical Biology

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A photoaffinity probe that targets folate-binding proteins

Cited by 4 publications

References 42 publications

Chemoproteomic Approaches for Unraveling Prokaryotic Biology

Chemoproteomic Approaches for Unraveling Prokaryotic Biology

Silyl Ether Enables High Coverage Chemoproteomic Interaction Site Mapping

Activity-based protein profiling in microbes and the gut microbiome

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