Editing Proteomics (section)

=== Protein Detection via Bioorthogonal Chemistry ===
[[File:Ketone-Aldehyde Condensation and Staudinger Ligations.svg|thumb|298x298px|Ketone and aldehyde mechanism with cell surface labeling. Staudinger ligations and their interaction with azide groups for labeling are shown in the second figure.]]
Recent advancements in [[bioorthogonal chemistry]] have revealed applications in protein analysis. The extension of using organic molecules to observe their reaction with proteins reveals extensive methods to tag them. [[Non-proteinogenic amino acids|Unnatural amino acids]] and various [[functional group]]s represent new growing technologies in proteomics.

Specific biomolecules that are capable of being metabolized in cells or tissues are inserted into proteins or glycans. The molecule will have an affinity tag, modifying the protein allowing it to be detected. Azidohomoalanine (AHA) utilizes this affinity tag via incorporation with Met-t-RNA synthetase to incorporate into proteins. This has allowed AHA to assist in determine the identity of newly synthesized proteins created in response to [[Perturbation (biology)|perturbations]] and to identify proteins secreted by cells.<ref>{{cite journal | vauthors = Eichelbaum K, Winter M, Berriel Diaz M, Herzig S, Krijgsveld J | title = Selective enrichment of newly synthesized proteins for quantitative secretome analysis | journal = Nature Biotechnology | volume = 30 | issue = 10 | pages = 984–990 | date = October 2012 | pmid = 23000932 | doi = 10.1038/nbt.2356 | s2cid = 2651429 }}</ref>

Recent studies<ref>{{cite journal | vauthors = Lang K, Chin JW | title = Bioorthogonal reactions for labeling proteins | journal = ACS Chemical Biology | volume = 9 | issue = 1 | pages = 16–20 | date = January 2014 | pmid = 24432752 | doi = 10.1021/cb4009292 }}</ref> using [[ketone]]s and [[aldehyde]]s condensations show that they are best suited for in vitro or [[Proximity labeling|cell surface labeling]]. However, using ketones and aldehydes as bioorthogonal reporters revealed slow kinetics indicating that while effective for labeling, the concentration must be high.

Certain proteins can be detected via their reactivity to [[Azide|azide groups]]. [[Non-proteinogenic amino acids]] can bear azide groups which react with phosphines in [[Staudinger reaction|Staudinger ligations]]. This reaction has already been used to label other biomolecules in living cells and animals.<ref>{{cite journal | vauthors = Devaraj NK | title = The Future of Bioorthogonal Chemistry | journal = ACS Central Science | volume = 4 | issue = 8 | pages = 952–959 | date = August 2018 | pmid = 30159392 | pmc = 6107859 | doi = 10.1021/acscentsci.8b00251 }}</ref>

The bioorthoganal field is expanding and is driving further applications within proteomics. It is worthwhile noting the limitations and benefits. Rapid reactions can create bioconjuctions and create high concentrations with low amounts of reactants. Contrarily slow kinetic reactions like aldehyde and ketone condensation while effective require a high concentration making it cost inefficient.