25055-84-9Relevant articles and documents
Non-natural amino acid and application thereof in protein site-specific modification and protein interaction
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Paragraph 0160-0162, (2021/02/13)
The invention relates to a non-natural amino acid compound represented by a general formula (I) and a preparation method thereof, and applications of the non-natural amino acid compound in fixed-pointmodification of bio-macro-molecular proteins, protein i
Photoaffinity palladium reagents for capture of protein-protein interactions
Zheng, Qizhen,Pang, Zhengyuan,Liu, Jingwei,Zhou, Yi,Sun, Yang,Yin, Zheng,Lou, Zhiyong
supporting information, p. 6369 - 6373 (2019/07/09)
Protein-protein interactions (PPIs) are indispensable in almost all cellular processes. Probing of complex PPIs provides new insights into the biological system of interest and paves the way for the development of therapeutics. Herein, we report a strategy for the capture of protein-protein interactions using photoaffinity palladium reagents. First, the palladium-mediated reagent site specifically transferred a photoaffinity modified aryl group to the designated cysteine residue. Next, the photoaffinity group was activated by UV radiation to trap the proximal protein residue for the formation of a crosslink. This strategy was used to capture the PYL-ABA-PP2C interaction, which is at the core of the abscisic acid (ABA) signalling pathway. Our results indicated that this palladium-mediated strategy can serve as an alternative for incorporating an increasing number of diverse substrates for protein crosslinking through cysteine modifications and can be explored for use in mapping protein-peptide or protein-protein interaction surfaces and in trapping potential interacting partners.
Mapping the protein interaction landscape for fully functionalized small-molecule probes in human cells
Kambe, Tohru,Correia, Bruno E.,Niphakis, Micah J.,Cravatt, Benjamin F.
supporting information, p. 10777 - 10782 (2014/08/18)
Phenotypic screening provides a means to discover small molecules that perturb cell biological processes. Discerning the proteins and biochemical pathways targeted by screening hits, however, remains technically challenging. We recently described the use of small molecules bearing photoreactive groups and latent affinity handles as fully functionalized probes for integrated phenotypic screening and target identification. The general utility of such probes, or, for that matter, any small-molecule screening library, depends on the scope of their protein interactions in cells, a parameter that remains largely unexplored. Here, we describe the synthesis of an ～60-member fully functionalized probe library, prepared from Ugi-azide condensation reactions to impart structural diversity and introduce diazirine and alkyne functionalities for target capture and enrichment, respectively. In-depth mass spectrometry-based analysis revealed a diverse array of probe targets in human cells, including enzymes, channels, adaptor and scaffolding proteins, and proteins of uncharacterized function. For many of these proteins, ligands have not yet been described. Most of the probe-protein interactions showed well-defined structure-activity relationships across the probe library and were blocked by small-molecule competitors in cells. These findings indicate that fully functionalized small molecules canvas diverse segments of the human proteome and hold promise as pharmacological probes of cell biology.
