A bifunctional amino acid to study protein–protein interactions

Yang, Tangpo; Li, Xin; Li, Xiang

doi:10.1039/d0ra09110c

Cited by 11 publications

(8 citation statements)

References 41 publications

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“…Crosslinks obtained after trypsin digestion were analyzed by the multidimensional MS to identify the specific amino acids involved in linking the glycine receptor to the cholesterol, which could subsequently map the cholesterol–protein interface altering as a function of cholesterol composition 47 . A bifunctional UAA bearing a diazirine, for photo‐crosslinking, and a terminal alkyne group, for bioorthogonal tagging, has been reported 42 . A ligand harboring the bifunctional UAA captured a target protein by photo‐crosslinking could then be tagged with an affinity motif such as biotin by alkyne‐azide click chemistry.…”

Section: Mapping Biological Interfaces By Clmsmentioning

confidence: 99%

“…47 A bifunctional UAA bearing a diazirine, for photocrosslinking, and a terminal alkyne group, for bioorthogonal tagging, has been reported. 42 A ligand harboring the bifunctional UAA captured a target protein by photo-crosslinking could then be tagged with an affinity motif such as biotin by alkyne-azide click chemistry. This strategy might enable the enrichment of ligand-target peptide conjugates after digestion and purification for high-resolution MS, allowing efficient mapping of biological interfaces on both sides of a ligand and a target.…”

Section: Interfaces Revealed By Uaa Incorporation and Crosslinking Co...mentioning

confidence: 99%

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Unveiling the biological interface of protein complexes by mass spectrometry‐coupled methods

Lim

2023

Proteins

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Most biomolecules become functional and bioactive by forming protein complexes through interaction with ligands that are diverse in size, shape, and physicochemical properties. In the complex biological milieu, the interaction is ligand-specific, driven by molecular sensing, and involves the recognition of a binding interface localized within a protein structure. Mapping interfaces of protein complexes is a highly sought area of research as it delivers fundamental insights into proteomes and pathology and hence strategies for therapeutics. While X-ray crystallography and electron microscopy remain the gold standard for structural elucidation of protein complexes, their artificial and static analytic nature often produces a non-native interface that otherwise might be negligible or non-existent in a biological environment. Recently, the mass spectrometry-coupled approaches, chemical crosslinking (CLMS) and hydrogen-deuterium exchange (HDMS) have become valuable analytic complements to the traditional techniques. These methods explicitly identify hot residues and motifs embedded in binding interfaces, especially when the interaction is predominantly dynamic, transient, and/or caused by an intrinsically disordered domain. Here, we review the principal role of CLMS and HDMS in protein structural biology with a particular emphasis on the contribution of recent examples to exploring biological interfaces. Additionally, we describe recent studies that utilized these methods to expand our understanding of protein complex formation and the related biological processes, to increase the probability of structure-based drug design.

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Section: Mapping Biological Interfaces By Clmsmentioning

confidence: 99%

Section: Interfaces Revealed By Uaa Incorporation and Crosslinking Co...mentioning

confidence: 99%

Unveiling the biological interface of protein complexes by mass spectrometry‐coupled methods

Lim

2023

Proteins

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“…Similarly, numerous photo affinity probes have also been recently reported and are known to be involved in protein-protein interactions. A bifunctional amino acid containing a terminal alkyne group and a diazirine as a photo-crosslinker was utilized for bio-orthogonal tagging (A bifunctional amino acid to study protein–protein interaction [ 114 ]. The most challenging part of biomolecular crosslinking is to retain their activity even after crosslinking.…”

Section: Chemical Crosslinking Of Proteinsmentioning

confidence: 99%

Insights on Chemical Crosslinking Strategies for Proteins

et al. 2022

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Crosslinking of proteins has gained immense significance in the fabrication of biomaterials for various health care applications. Various novel chemical-based strategies are being continuously developed for intra-/inter-molecular crosslinking of proteins to create a network/matrix with desired mechanical/functional properties without imparting toxicity to the host system. Many materials that are used in biomedical and food packaging industries are prepared by chemical means of crosslinking the proteins, besides the physical or enzymatic means of crosslinking. Such chemical methods utilize the chemical compounds or crosslinkers available from natural sources or synthetically generated with the ability to form covalent/non-covalent bonds with proteins. Such linkages are possible with chemicals like carbodiimides/epoxides, while photo-induced novel chemical crosslinkers are also available. In this review, we have discussed different protein crosslinking strategies under chemical methods, along with the corresponding crosslinking reactions/conditions, material properties and significant applications.

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“…[154] A compact bifunctional alkyl diazirine UAA with an alkyne was developed and incorporated into peptides. [155] A UAA containing an aryl tetrazole has also been developed, reportedly having higher crosslinking levels than benzophenone alternatives. [127] The Chen lab has also developed several bifunctional UAA's for studying protein-protein interactions, including a cleavable Se amino acid with an alkyl diazirine and an alkyne.…”

Section: Pal In Unnatural Amino Acids For Protein-protein Interactionsmentioning

confidence: 99%

Photoaffinity Labeling Chemistries Used to Map Biomolecular Interactions

West

Woo

2022

Israel Journal of Chemistry

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Photoaffinity labeling (PAL) is one of the few biochemical techniques that can give direct evidence of biomolecular interactions in cells. Several photoactivatable functional groups have been adapted for use in PAL since its first implementation. The diversity of these chemistries has expanded the scope and fidelity of PAL experiments, but also increased the considerations during PAL probe design. In this review, we describe the major chemistries used in PAL experiments and their relative benefits and disadvantages. We additionally discuss recent examples of PAL experiments and provide recommendations on how to design a PAL probe.

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A bifunctional amino acid to study protein–protein interactions

Abstract: dzANA is a novel bifunctional (photo-reactive and bioorthogonal) amino acid to study protein–protein interactions.

Cited by 11 publications

References 41 publications

Unveiling the biological interface of protein complexes by mass spectrometry‐coupled methods

Unveiling the biological interface of protein complexes by mass spectrometry‐coupled methods

Insights on Chemical Crosslinking Strategies for Proteins

Photoaffinity Labeling Chemistries Used to Map Biomolecular Interactions

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